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.
Background & Aims: The aim of this study was to investigate if the variable outcome of chronic hepatitis B may be related to hepatitis B virus (HBV) genotype. Methods: The clinical and virologic ...events observed over prolonged follow-up in 258 Spanish patients with chronic hepatitis B infected with different genotypes of HBV were compared. Results: The prevalence of genotype A, D, and F was 52%, 35%, and 7%, respectively. Concomitant sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A– than in genotype D– (log-rank, 14.2; P = 0.002) or genotype F–infected patients (log-rank, 4.2; P = 0.03). The rate of hepatitis B surface antigen (HBsAg) clearance was higher in genotype A than in genotype D hepatitis (log-rank, 4.6; P = 0.03). Sustained remission and clearance of HBsAg were associated with infection with genotype A by Cox regression analysis. Seroconversion to antibody to hepatitis B e antigen (anti-HBe) was unrelated to HBV genotype, but the rate of sustained remission after seroconversion was higher in genotype A than in genotype D hepatitis both in patients who seroconverted to anti-HBe during follow-up (log-rank, 4.5; P = 0.03) and in patients with positive anti-HBe at baseline (log-rank, 6.66; P = 0.009). Death related to liver disease was more frequent in genotype F than in genotype A (P = 0.02) or genotype D (P = 0.002) hepatitis. Conclusions: The long-term outcome of chronic hepatitis B is different in patients infected with HBV genotype A, D, or F.
GASTROENTEROLOGY 2002;123:1848-1856
We describe the clinical characteristics, the patterns of association, and the role of antiviral therapies in patients with sarcoidosis associated with chronic hepatitis C virus (HCV) infection. ...Sixty-eight patients were included in the current study, 56 cases identified in the literature search plus 12 unpublished cases from our department. In 50 HCV patients, sarcoidosis appeared after starting antiviral therapy. Antiviral therapy associated with triggered sarcoidosis consisted of alpha-interferon monotherapy in 20 cases and combined therapy with alpha-interferon and ribavirin in 30. Sarcoidosis appeared during the first 6 months after starting therapy in 66% of patients. The clinical picture of sarcoidosis included predominantly pulmonary disease in 38 (76%) patients and cutaneous sarcoidosis in 30 (60%). Antiviral therapy was discontinued in 60% of patients and continued or adjusted in 14%, while sarcoidosis appeared after completed therapy in the remaining cases. Specific therapy for sarcoidosis was started in only 21 patients, mainly with oral corticosteroids. The outcome of patients was detailed in 46 cases: remission or improvement was observed in 38/46 (83%) patients, stabilization of sarcoidosis in 5/46 (11%), and reactivation of sarcoidosis after an initial improvement in 3/46 (6%). Finally, 18 treatment-naive HCV patients presented sarcoidosis, with 14/18 (87%) patients presenting with pulmonary involvement and 8/18 (44%) with cutaneous involvement. In summary, sarcoidosis may be observed in HCV patients in 2 different situations: triggered by antiviral therapy (in 75% of cases) and unrelated to treatment. Sarcoidosis during antiviral therapy may present mainly as cutaneous or pulmonary disease, with a benign, uncomplicated evolution in more than 85% of cases. However, more complicated cases are observed, especially in HCV patients with preexisting sarcoidosis and/or with previous antiviral treatment. Clinicians should be aware of the possibility that sarcoidosis may initially manifest or be reactivated during or shortly after treatment with antiviral therapy in patients with chronic HCV infection.
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.
Summary
Background Patients infected with hepatitis C virus genotype 1 who are true non‐responders to previous therapy suffer from a very difficult‐to‐cure disease. New approaches to treatment are ...necessary.
Aim To explore the efficacy, pharmacokinetics and safety of fixed‐dose induction with peginterferon α‐2a and ribavirin in this difficult‐to‐cure population.
Methods Seventy‐five hepatitis C virus genotype 1 true non‐responder patients to a previous interferon‐based combination regimen were randomised to receive peginterferon α‐2a 360, 270 or 180 μg/week for 12 weeks, followed by 180 μg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon α‐2a concentration was measured throughout the study.
Results Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 μg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration‐time curve of peginterferon α‐2a from 0–12 weeks increased in a dose‐dependent manner (P < 0.0001) and was associated with the sustained virological response (odds ratio: 1.35; 95% CI: 0.89, 2.06). The three regimens were equally well tolerated.
Conclusion Fixed‐dose induction of peginterferon α‐2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non‐responder patients.
Current therapies for chronic hepatitis C virus (HCV) in HIV co-infected patients have a low success rate and are poorly tolerated. We have evaluated the efficacy and safety of interferon alfa-2b ...(IFN) + ribavirin (RBV) versus pegylated interferon alfa-2b (PEG-INF) + RBV.
Randomized, single-centre, open-label clinical trial including patients with: detectable HCV-RNA, alanine aminotransferase > 1.5-fold upper limit of normal, abnormal liver histology, CD4 cell count > 250 x 10/l and HIV RNA < 10 000 copies/ml. Patients were assigned to INF (3 x 10 units three times/week) or PEG-IFN (100-150 microg/week) plus RBV (800-1200 mg/day). Duration of treatment was 48 weeks (only 24 weeks for HCV genotypes 2 or 3 and baseline HCV RNA < 800 000 IU/ml). The primary endpoint was a sustained virological response (SVR).
Ninety-five patients were randomized (43 INF + RBV, 52 PEG-INF + RBV), 68% males, 82% injecting drug users; 63% genotypes 1 or 4 and 36% genotypes 2 or 3; 62% fibrosis index grade >/=2 and 30% bridging fibrosis/cirrhosis. SVR was significantly higher in the PEG-INF + RBV arm, 44% versus 21% (intent to treat; P = 0.017). Among patients with genotypes 1 or 4, SVR were 38% versus 7% (P = 0.007) and 53% versus 47% (P = 0.730) for genotypes 2 or 3. CD4 cell count but not its percentage dropped in both arms and HIV RNA viral load did not change from baseline. Side effects were very frequent in both arms leading to treatment discontinuation in 14 patients without statistical differences between arms (P = 0.565).
PEG-INF + RBV was significantly more effective than INF + RBV for the treatment of chronic hepatitis C in HIV co-infected patients, mainly of genotype 1 or 4.
Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort ...study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C. (H
EPATOLOGY 2002;36:986-992.)
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