Transplantation of organs from donors infected with hepatitis C virus presents an opportunity to identify those individuals most likely to benefit from directly active antiviral therapies as well as ...possible limitations of these therapies in transplant recipients. See the meeting report from Levitsky et al on page 2790.
Summary
Portal hypertension is a predictor of liver‐related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon‐free hepatitis C treatment on portal ...pressure is unknown. Fifty patients with Child‐Pugh‐Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient HVPG >6 mm Hg) were randomized to receive 48 weeks of open‐label sofosbuvir plus ribavirin at Day 1 or after a 24‐week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by ‐1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow‐up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long‐term follow‐up. (EudraCT 2012‐002457‐29).
Summary
Background
Grey Zone (GZ) is an ill‐defined situation including patients falling between inactive carrier (IC) state and HBeAg‐negative chronic hepatitis B (HBeAg‐negative CHB).
Aims
To ...assess the long‐term outcomes of GZ patients compared to IC in the absence of treatment.
Methods
Retrospective analysis of 287 IC and GZ HBeAg‐negative patients. Patients were classified into 4 groups at baseline: HBV‐DNA <2000 IU/mL and ALT <40 U/L (IC), HBV‐DNA <2000 IU/mL and ALT 40‐80 U/L (GZ‐1), HBV‐DNA 2000‐20 000 IU/mL and ALT <40 U/L (GZ‐2) or ALT 40‐80 U/L (GZ‐3). Data were also analysed using AASLD ALT criteria.
Results
After a median follow‐up of 8.2 (5‐19) years, HBsAg loss occurred in about 15% ICs or GZ patients. Transition into IC state occurred in 40% of GZ patients. DNA fluctuations >2000 IU/mL correlated inversely with transition into IC and HBsAg loss. HBsAg levels were significantly lower in ICs than in GZ patients (338 IU/mL 20‐3269 vs 5763 IU/mL 2172‐17 754; P < 0.05). Among the latter group, there was an increasing gradient of HBsAg levels from GZ‐1 to GZ‐3 patients (P < 0.05). HBeAg‐negative CHB occurred in only 18 (6.3%) GZ patients. No patient developed cirrhosis nor advanced fibrosis. ALT/HBV‐DNA fluctuations and HBeAg‐negative CHB development were more frequent in genotype B/C patients, whereas HBsAg loss occurred only in genotype A/D patients.
Conclusions
Most Caucasian GZ patients present excellent long‐term outcomes in the absence of treatment, with a high rate of HBsAg loss and low rate of progression to HBeAg‐negative CHB. HBV‐genotyping and HBsAg levels could help to predict outcomes and better classify GZ patients.
Linked ContentThis article is linked to Ridruejo paper. To view this article visit https://doi.org/10.1111/apt.14644.
IL28B gene polymorphisms are associated with the response to antiviral therapy in hepatitis C patients. We investigated the influence of IL28B polymorphisms on the response to therapy before and ...after liver transplantation (LT). Genotyping of SNPs rs8099917 and rs12979860 was performed in 128 HCV‐infected liver transplant recipients and in their donors; all patients underwent antiviral treatment after LT. The prevalence of genotypes rs12979860CC and rs8099917TT was higher in donors than in recipients (50% vs.19%, p < 0.001 and 67% vs. 38%, p < 0.001, respectively). Response to antiviral therapy was significantly higher for recipient genotype rs12979860CC as compared to rs12979860CT/TT both before (100% vs. 48% p = 0.013) and after LT (59% vs. 25% p = 0.002). The figures were almost identical for SNP rs8099917. Sustained virological response after LT was particularly high in patients with favorable recipient and donor genotypes (p < 0.01 for both SNPs). In a subgroup of 34 patients treated while awaiting LT, a favorable donor IL28B genotype was associated with an improved virological response after LT. Our results support a major role of recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence. Interestingly, donor genotype also seems to influence the response pattern, especially in recipients who have a favorable IL28B genotype.
These results support a major role for the recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence after liver transplantation, while the donor genotype seems to exert a positive effect in recipients who have a favorable IL28B genotype.
Summary
Background
A few cases of hepatitis B virus (HBV) reactivation during anti‐viral therapy against hepatitis C (HCV) have been reported. However, the information regarding the real impact of ...this phenomenon is scarce.
Aim
To evaluate the risk of HBV reactivation during anti‐viral therapy against HCV with an interferon‐free regimen with direct‐acting anti‐virals (DAAs).
Methods
Observational and prospective study of 352 patients receiving DAAs therapy between September 2015 and May 2016. HBV‐DNA and ALT levels were monitored at baseline, at week 4 of anti‐viral therapy, at end of treatment and 12 weeks after treatment discontinuation in patients with HBV surface antigen (HBsAg) positive or HBV core antibody (anti‐HBc) positive before starting anti‐viral therapy.
Results
Ten (2.8%) and 64 (18%) patients were HBsAg and anti‐HBc positive at baseline, respectively. Five (50%) of 10 HBsAg positive and one (1.6%) of 64 anti‐HBc positive patients presented HBV virological reactivation (>1log increase in HBV‐DNA levels). None of these patients presented clinical reactivation (increase in ALT levels).
Conclusions
HBV virological reactivation is frequent in HBsAg+ patients receiving anti‐viral therapy against HCV. However, HBV‐DNA elevations were modest (<20 000 IU/mL) and without clinical impact (no ALT elevation).
Linked ContentThis article is linked to Londoño et al, Huang et al, Chen, Wang and Kao, Hsu et al papers. To view these articles visit https://doi.org/10.1111/apt.14104, https://doi.org/10.1111/apt.14080, https://doi.org/10.1111/apt.14051, https://doi.org/10.1111/apt.14116 and https://doi.org/10.1111/apt.14127.
The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C–infected and ...48 non–hepatitis C virus (HCV)‐infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p < 0.001). Five‐year graft and patient cumulative survival were 90% and 92% in patients with LSM < 8.7 kPa (p < 0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p < 0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non‐HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C‐related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.
The authors report the excellent accuracy of transient elastography one year after liver transplantation to predict long‐term hepatitis C–related clinical outcomes, which are significantly improved in patients with high liver stiffness who respond to antiviral therapy.
Summary
Background
Chronic hepatitis C is considered a systemic disease because of extra‐hepatic manifestations. Neuroimaging has been employed in hepatitis C virus‐infected patients to find in vivo ...evidence of central nervous system alterations.
Aims
Systematic review and meta‐analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C.
Methods
Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer‐reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis C patients without cirrhosis or encephalopathy, with control group. Meta‐analyses were performed when possible.
Results
The final sample comprised 25 studies (magnetic resonance spectroscopy N = 12, perfusion weighted imaging N = 1, positron emission tomography N = 3, single‐photon emission computed tomography N = 4, functional connectivity in resting state N = 1, diffusion tensor imaging N = 2 and structural magnetic resonance imaging N = 2). The whole sample was of 509 chronic hepatitis C patients, with an average age of 41.5 years old and mild liver disease. A meta‐analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference MD 0.12, 95% confidence interval CI 0.06‐0.18), creatine (MD 0.85, 95% CI 0.42‐1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39‐2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07‐0.19) in chronic hepatitis C patients compared with healthy controls. Photon emission tomography studies meta‐analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis C patients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies.
Conclusions
Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances.
Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. ...Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren's syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.
Aliment Pharmacol Ther 2011; 33: 138–148
Summary
Background Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C.
Aim To validate and compare the diagnostic ...performance of non‐invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment.
Methods The performances of Forns’ score, AST to platelet ratio index (APRI), FIB‐4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients.
Results Forns’ score, APRI, FIB‐4 and ELF score showed comparable diagnostic accuracies for significant fibrosis area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively. To identify cirrhosis, FIB‐4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non‐1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR.
Conclusions Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.
Introduction
Chronic Hepatitis C infection is considered a systemic disease with extrahepatic manifestations, mainly neuropsychiatric symptoms
,
which is associated with a chronic low-grade ...inflammatory state
.
Hepatitis C virus (HCV) eradication is currently achieved in >98% of cases with oral direct-acting antivirals (DAA).
Objectives
To study potential clinical neuropsychiatric changes (mood, cognition, sleep, gastrointestinal, sickness, and motion) in HCV-infected patients after HCV eradication with DAA.
Methods
Design: Cohort study. Subjects: 37 HCV-infected patients, aged<55 years old, with non-advanced liver disease receiving DAA; free of current mental disorder. 24 healthy controls were included at baseline. Assessment: -Baseline (BL) (socio-demographic and clinical variables, MINI-DSM-IV, and Neurotoxicity Scale (NRS), (mood, cognitive, sleep, gastrointestinal, sickness and motor dimensions). Follow-up: End-of-treatment, 12weeks-after and 48weeks-after DAA: NRS. Analysis: Descriptive and bivariate non-parametrical analysis.
Results
NRS total score and dimensions where different between cases and controls (.000) at baseline. NRS total score (.000) and mood (.000), cognition (.000), sleep (.002), gastrointestinal (.017), and sickness (.003), except motor dimension score (.130) showed significant longitudinal improvement.
Conclusions
HCV-infected patients with mild liver disease presented significantly worse scores for neurotoxicity symptomatology in all dimensions compared to healthy individuals. After HCV eradication with DAA, both at short and long follow-up a significant improvement of the NRS total score and each of the dimensions (except motor) were observed. However, they did not reach the values of healthy individuals, suggesting a not complete neuropsychiatric restoration in the period studied. Grant: ICIII-FIS:PI17/02297.(One way to make Europe) (RMS) and Gilead Fellowship-GLD17/00273 (ZM); and the support of SGR17/1798 (RMS)
Disclosure
No significant relationships.
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