Successful Treatment Of Chronic Hepatitis Research Articles

Non-invasive quantification of liver fibrosis regression following successful treatment of chronic hepatitis C with direct acting antivirals

Abstract Introduction. The past years have revolutionized the treatment of hepatitis C virus (HCV) infection, with high rates of sustained virologic response (SVR). Furthermore, liver fibrosis has recently been redefined as a dynamic, reversible process. Methods. We performed a prospective cohort study to assess the role of laboratory evaluations and non-invasive measurement of liver stiffness in establishing the right time for starting treatment and in assessing the regression of liver fibrosis in Romanian patients treated with direct acting antivirals (DAA) for genotype 1b chronic hepatitis C. Results. We present the results for 102 patients, with a mean age of 58.5 years, and a rate of SVR of 100%. Our study has ruled out older age (p=0.628), IL28B non-CC genotype (p=0.693), baseline viral load above the cutoff of 600,000 IU/mL (p=0.353), and the presence of diabetes mellitus (p=0.272) or baseline steatosis (p=0.706) as factors potentially influencing the regression of liver fibrosis following DAA treatment of HCV infection with the 3D regimen. The quantitative regression of liver stiffness was inversely correlated with the duration of HCV infection (p=0.017), suggesting that timely treatment might associate better outcomes in terms of liver fibrosis. Conclusion. Our study’s results point towards the need to start DAA treatment earlier in patients with HCV infection.

Successful Treatment of Chronic Hepatitis C Infection With Directly Acting Antivirals in Renal Transplant Recipients

Aims The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. 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. Methods 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 twelve 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 was analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. Results The median baseline HCV RNA concentration in the whole group was 7.38 x 106 IU/ml (1.23 x 104- 6.36 X 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 5 (10.64%) patients. The only serious adverse effect was anemia observed in 8 (57%) patients in the Sofosbuvir and Ribavirin group. Conclusion 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.

ANTI AQUAPORIN 4 POSITIVE NEUROMYELITIS OPTICA SPECTRUM DISORDER AND PRIMARY SJÖGREN SYNDROME FOLLOWING SUCCESSFUL THERAPY FOR CHRONIC HEPATITIS C – REPORT OF A CLINICAL CASE

Neuromyelitis optica spectrum disorders (NMOSD) are a heterogeneous group of potentially disabling central nervous system inflammatory disorders. Association with other organ-specific or multisystem autoimmune disorders is commonly encountered. We report the case of a Caucasian woman with AQP4-IgG positive NMOSD and primary Sjögren syndrome - previously reported as a poster at the 14th Congress of the Romanian Society of Neurology (abstract published in ROJN, Vol. XV, Suppl). The clinical onset followed the successful treatment of chronic hepatitis C with interferon alpha and ribavirin. To the best of our knowledge, similar clinical presentations have not been described. The etiopathogenic treatment included high dose methylprednisolone, immune suppression with cyclophosphamide, and periodic plasma exchanges. In spite of an active disease with very high baseline AQP4-IgG titres, during the four years of treatment the patient has had only one relapse and has no residual disability.

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

Treatment of chronic hepatitis C virus (HCV) infection after renal allograft transplantation has been an obstacle because of contraindications associated with IFN-based therapies. Direct-acting antiviral agents are highly efficient treatment options that do not require IFN and may not require ribavirin. Therefore, we assessed the efficacy and safety of sofosbuvir and ledipasvir in renal transplant patients with chronic HCV infection. Fifteen renal allograft recipients with therapy-naive HCV genotype (GT) 1a, 1b, or 4 were treated with the combination of sofosbuvir and ledipasvir without ribavirin for 8 or 12 weeks. Clinical data were retrospectively analyzed for viral kinetics and for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, laboratory values, and potential adverse effects. Ten patients (66%) exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 4; HCV GT1b, n = 6). The other 5 patients exhibited a virologic response within 8 (HCV GT 1b, n = 4) or 12 weeks (HCV GT4, n = 1). One hundred percent of patients exhibited sustained virologic response at week 12 after the end of treatment. Clinical measures of liver function improved substantially for all patients. Adverse events were scarce; renal transplant function and proteinuria remained stable. Importantly, dose adjustments for tacrolimus were necessary for maintaining sufficient trough levels. The described regimen appears to be safe and effective for patients after renal transplant and is a promising treatment regimen for eradicating HCV in this patient population.

Successful Treatment of Chronic Hepatitis C using Pegylated Interferon and Ribavirin in a Patient with Sheehan's Syndrome

A 50-year-old female with Sheehan's syndrome was treated for chronic hepatitis C using pegylated interferon-α2b and ribavirin. The patient's HCV-RNA status was negative by the fourth week and remained undetectable until the completion of treatment without signs that Sheehan's syndrome had been exaggerated. This case demonstrates that pegylated interferon-α2b and ribavirin does not necessarily exacerbate Sheehan's syndrome.

Successful treatment of chronic hepatitis C virus genotype 1b infection of a patient with compensated cirrhosis after renal transplantation using daclatasvir-asunaprevir combination therapy: a case report and literature review

Hepatitis C virus (HCV) infection a major disorder that is not only a liver-related disease but also a cardiovascular complication in renal transplant recipient. Interferon-based therapy is a contraindication after transplantation because interferon is possibly induced to graft rejection. Only limited anecdotal evidence exists on the antiviral efficacy and tolerability of HCV direct acting antivirals (DAAs) in patients with chronic kidney disease (CKD), including renal transplant recipients. Then, we report a successful treatment case of chronic hepatitis C virus genotype 1b infection in a patient with compensated cirrhosis after renal transplantation using daclatasvir-asunaprevir combination therapy and reviewed the literature. A 64-year-old female renal transplantation (RT) recipient complicated with compensated cirrhosis due to hepatitis C virus (HCV) genotype 1b infection was treated with interferon (INF)–ribavirin-free combinations of DAAs such as daclatasvir plus asunaprevir. She was medicated with daclatasvir 60 mg once a day and asunaprevir 100 mg twice a day for 24 weeks. Her initial HCV RNA was log10 6.2 IU/ml, and HCV RNA was not detected from 10 weeks. She achieved a sustained virological response at 24 weeks (SVR24). During this therapy, her serum creatinine and tacrolimus trough level were slightly elevated, but those abnormalities were returned to the basal level by decreasing the dose of extended-release tacrolimus. No other adverse event requiring discontinuation of the treatment occurred. Almost all DAA treatments of HCV infection in renal transplant recipients have been sofosbuvir-based antiviral treatment, but we considered that daclatasvir-asunaprevir combination therapy is suitable to renal-impaired recipient because sofosbuvir is contraindicated in patients whose estimated GFR is <30 ml/min/1.73 m2, and both of daclatasvir and asunaprevir are mainly primarily metabolized by the liver. We showed excellent effect daclatasvir-asunaprevir combination therapy to a renal transplant recipient with chronic HCV infection and reviewed the literature.

Successful treatment of chronic hepatitis c virus infection in kidney transplant recipients with directly acting antiviral agents – Single centre experience

Successful treatment of chronic hepatitis c virus infection in kidney transplant recipients with directly acting antiviral agents – Single centre experience

Diabetes and Cirrhosis Are Risk Factors for Hepatocellular Carcinoma After Successful Treatment of Chronic Hepatitis C.

Successful treatment of hepatitis C virus (HCV) infection reduces the risk for hepatocellular carcinoma (HCC), but a risk remains. Current guidelines recommend continued HCC surveillance after sustained virologic response (SVR) has been achieved. This study aimed to investigate risk factors and incidence rates for HCC after SVR in HCV patients with pretreatment advanced liver disease (Metavir stage F3/F4). All patients with advanced liver disease successfully treated for HCV at Karolinska University Hospital during 1992-2013 (n = 399) were followed up for a median of 7.8 years. Data from national registries were used to minimize loss to follow-up. Incidence rates and hazard ratios (HRs) for development of HCC were calculated by Cox regression analysis. Seventeen patients developed HCC during 3366 person-years (PY) of follow-up. The HCC incidence rate was 0.95 (95% confidence interval [CI], .57-1.6) and 0.15 (95% CI, .05-.49) per 100 PY for patients with pretreatment F4 and F3, respectively. Patients with pretreatment cirrhosis and diabetes had a HR to develop HCC of 6.3, and an incidence rate of 7.9 per 100 PY (95% CI, 3.3-19) during the first 2 years of follow-up. The risk for HCC decreased significantly 2 years after SVR had been achieved. Diabetes mellitus and cirrhosis are strong risk factors for HCC development after SVR has been achieved. The risk to develop HCC diminishes significantly 2 years after SVR. Patients without cirrhosis have a low risk to develop HCC after SVR, and the benefit of HCC surveillance for this group is questionable.

Successful Treatment of Chronic Hepatitis C Infection With Direct-Acting Antivirals in a Heart Transplant Recipient: A Case Report

BackgroundHeart transplant (HT) recipients with chronic hepatitis C virus (HCV) infection are noted to have higher rates of HCV related morbidity and mortality. Treatment of HCV in the past was fraught with low cure rates, increased risk of graft rejection, and medication-related side effects. Case ReportWe report a case of successful treatment of HCV infection in a HT recipient. The patient was found to have HCV during his pretransplant workup. He underwent uneventful orthotopic HT in 2000. The HCV infection was monitored with regular liver enzymes and the surveillance liver biopsies at 2 and 5 years after HT showed mild but stable liver disease, and he stayed on chronic immunosuppression. He was not offered interferon-based HCV therapy because of the risk of steroid-resistant graft failure and cardiac decompensation. With the availability of the new direct-acting antivirals (DAA) for HCV infection, and worsening of liver fibrosis on noninvasive testing, we treated him with sofosbuvir and simeprevir for 12 weeks. During treatment, he remained clinically stable from a cardiac standpoint and he showed biochemical improvement in his liver and renal functions. Tacrolimus levels remained stable and did not require any dose adjustment. He showed rapid virologic response and subsequently achieved sustained virologic response at 12 weeks. ConclusionDAA use was safe and effective in treating HCV infection in a HT recipient.

Successful treatment of chronic hepatitis C with triple therapy in an opioid agonist treatment program

BackgroundPeople who inject drugs (PWID) constitute 10 million people globally with hepatitis C virus, including many opioid agonist treatment patients. Little data exist describing clinical outcomes for patients receiving HCV treatment with direct-acting antiviral agents (DAAs) in opioid agonist treatment settings. MethodsIn this retrospective observational study, we describe clinical outcomes for 50 genotype-1 patients receiving HCV treatment with triple therapy: telaprevir (n=42) or boceprevir (n=8) in combination with pegylated interferon and ribavirin on-site in an opioid agonist treatment program. ResultsOverall, 70% achieved an end of treatment response (ETR) and 62% achieved a sustained virological response (SVR). These treatment outcomes are nearly equivalent to previously published HCV outcomes shown in registration trials, despite high percentages of recent drug use prior to treatment (52%), ongoing drug use during treatment (45%) and psychiatric comorbidity (86%). Only 12% (n=6) discontinued antiviral treatment early for non-virological reasons. Four patients received a blood transfusion, and one discontinued telaprevir due to severe rash. ConclusionsThese data demonstrate that on-site HCV treatment with direct-acting antiviral agents is effective in opioid agonist treatment patients including patients who are actively using drugs. Future interferon-free regimens will likely be even more effective. Opioid agonist treatment programs represent an opportunity to safely and effectively treat chronic hepatitis C, and PWID should have unrestricted access to DAAs.

MicroRNA expression in hepatocellular carcinoma after the eradication of chronic hepatitis virus C infection using interferon therapy.

Hepatocellular carcinoma (HCC) develops in up to 5% of patients after the successful treatment of chronic hepatitis C virus (HCV) infection using interferon therapy. The aim of this study was to characterize miRNA expression in liver tissues from patients who achieved a sustained viral response (SVR). Seventy-one patients with resected HCC were enrolled into the present study: 61 HCC from patients with continuously infected HCV (HCV-HCC) and 10 from patients who had achieved SVR (SVR-HCC). We also included non-tumor tissues (SVR-NT) from four patients with SVR-HCC, and liver tissue (SVR-CH) from four SVR patients without HCC. Total RNA was extracted from liver samples. The miRNA expression patterns were analyzed using microarrays. In addition, target gene expression was quantified after miRNA overexpression in HEK293 cells. We could discriminate between SVR-HCC and HCV-HCC with 75.36% accuracy using the expression pattern of six specific miRNA. The expression levels of 37 miRNA were significantly lower in HCV-HCC than in SVR-HCC, whereas the expression of 25 miRNA was significantly higher in HCV-HCC than SVR-HCC (P < 1.0E-05). The expression of thrombospondin 1 was regulated in an opposing manner by miR-30a-3p in SVR-HCC and HCV-HCC. In non-tumor tissues, the expression pattern of seven miRNA could distinguish between SVR-CH and SVR-NT with 87.50% accuracy. Comprehensive miRNA expression analyses could not only differentiate between SVR-HCC and HCV-HCC but also forecast hepatocarcinogenesis after achieving SVR.

Evidence for immune activation in patients with residual hepatitis C virus RNA long after successful treatment with IFN and ribavirin.

Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52-66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1β were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.

Sustained Virologic Response for Chronic Hepatitis C Infection after 27 Days of Treatment with Sofosbuvir and Ribavirin.

Successful treatment of chronic hepatitis C virus infection can now be achieved using direct-acting antiviral agents without interferon. In this report, we present a patient who achieved a sustained virologic response after 27 days of treatment with sofosbuvir and ribavirin. It is imperative to identify factors that allow for shorter treatment times in some individuals.

New-onset ascites as a manifestation of virologic relapse in patients with hepatitis C cirrhosis

BackgroundChronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation.CaseIn this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse.ConclusionWe propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.

Persistence of Hepatitis C Virus during and after Otherwise Clinically Successful Treatment of Chronic Hepatitis C with Standard Pegylated Interferon α-2b and Ribavirin Therapy

Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12–88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity <2 IU/mL. Clone sequencing of the HCV 5′-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8 of 9 patients during therapy, although only 5.4% plasma samples were positive by clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20 (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive strand collected during or after treatment. Pre-treatment point mutations persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment.

Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication

Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2′-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae.

Successful treatment of chronic hepatitis B and D with pegylated-interferon plus entecavir

Interferon-based regimen has been used to treat hepatitis D virus (HDV) super-infection on top of hepatitis B virus (HBV) carriers; however, viral relapse is frequent after stopping therapy. Recently, quantitative hepatitis B surface antigen (qHBsAg) was introduced to help the management of chronic hepatitis B (CHB). Little is known about its role in the treatment of HBV and HDV dual infection. Herein, we reported a 45-year-old male HBV carrier with HDV co-infection who received combination therapy of pegylated-interferon α-2a plus entecavir. The qHBsAg level was adopted as the treatment guidance and a consolidation therapy of 12 months was continued after HBsAg loss. The patient achieved HBsAg seroconversion with HDV RNA undetectable after 35 months of combination therapy and sustained therapeutic response 12 months post-therapy. Therefore, personalized response-guided therapy by using qHBsAg may be an option for the treatment for HBV and HDV dual infection.

Hepatitis C treatment with triple therapy in a patient with hemophilia A

We report a case of successful treatment of chronic hepatitis C infection with telaprevir-based triple therapy in a patient with hemophilia A complicated by factor VIII inhibitor. A twenty-two years old male with hereditary hemophilia A and high-titer factor VIII inhibitor was taking maintenance doses of recombinant factor VIII. He visited our clinic for treatment of his chronic hepatitis C with the newly instituted protease inhibitor based therapy. He was diagnosed with hepatitis C genotype 1a at one year of age. He was initiated on telaprevir, ribavirin and peg-interferon for treatment of hepatitis C and qualified for response-guided therapy. He completed treatment at 24 wk with minimal adverse effects. Notably, after 4 wk of hepatitis C treatment, his factor VIII inhibitor screen was negative and the dose for recombinant factor VIII decreased by half of the initial dosing before he was treated for hepatitis C. We suspect that suppressing hepatitis C may help decrease factor VIII inhibitor level and the need for recombinant factor VIII.

Severe transaminitis after interferon–ribavirin therapy in HIV/HCV‐coinfected patients: influence of a sustained HCV response

Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis.

Safety evaluation of telbivudine

Importance of the field: Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects. Telbivudine is one of the more potent options available, with a 6.5- to 6.6-log copies/ml hepatitis B DNA reduction at 12 weeks in an early viral kinetic study, a potency comparable to entecavir. It is also one of the few drugs in the treatment of CHB under FDA pregnancy Category B.Areas covered in this review: The efficacy and safety profile of telbivudine in compensated and decompensated CHB patients compared to other agents are discussed. Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in telbivudine treatment are reviewed. Infrequent but significant adverse effects of other nucleoside/nucleotide analogs are highlighted.What the reader will gain: Readers are provided the latest update on the clinical profile of long-term use of telbivudine.Take home message: Long-term telbivudine treatment offers effective viral suppression to CHB patients with certain baseline characteristics and on-treatment virologic response. Creatine kinase elevation is not a good predictor of muscle-related adverse effects with nucleoside/nucleotide analogs. But significant myopathy and neuropathy have been reported in a small number of patients receiving telbivudine.