A. Ippolito

Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis.

Background  Anti‐viral therapy seems more successful in HCV genotype 2 than genotype 3‐infected patients.

Outcome of chronic delta hepatitis in Italy: a long-term cohort study.

BACKGROUND & AIMS To investigate the impact of HDV infection on morbidity and mortality of patients. PATIENTS AND METHODS This was a retrospective study on 188 patients that underwent a program of periodic surveillance until 2008. The demographic data, stage of liver disease, treatment efficacy, development of liver complications (ascites, oesophageal bleeding, encephalopathy), and survival were registered. A Cox regression analysis was carried out to determine the impact of viral and patient features on survival. RESULTS At baseline, 126 patients (67%) tested positive for serum IgM anti-HDV antibodies, 171 (91%) for anti-HBe, 175 (93%) for serum HDV-RNA, and 61 (33%) for serum HBV-DNA. Eighty-two patients (43%) had chronic hepatitis at histology; the remaining 106 individuals had a clinical/histological diagnosis of cirrhosis. Ninety-six patients received interferon (n = 90) or lamivudine (n = 6) therapy, and 27 of them (30%) attained a sustained response. During follow up, 21 patients with chronic hepatitis progressed to cirrhosis. Of the 127 cirrhotic patients, hepatic decompensation occurred in 42 patients (33%) and hepatocellular carcinoma in 17 (13%). The 5- and 10-year survival free of events were 96.8% and 81.9%, respectively, for patients with chronic hepatitis, and 83.9% and 59.4% for cirrhotics (p<0.01). At multivariate analysis, lack of antiviral therapy (p = 0.01), cirrhosis at presentation (p<0.01), and male sex (p = 0.03) independently predicted a worse outcome. CONCLUSION HDV liver disease lasts several decades. Half of all patients who develop cirrhosis later will advance to liver failure. At present, interferon therapy is recommended as soon as possible to slow or alter the natural course of liver disease.

Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin

BACKGROUND & AIMS The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. RESULTS Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637-7.101), low (<400,000 IU) viremia (OR 2.907; CI 2.111-4.004), F0-F2 fibrosis (OR 1.631; CI 1.122-2.372) and type 2 diabetes (OR 0.528; CI 0.286-0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274-9.208), IL28B CC genotype (OR 3.306; CI 2.301-4.751), low viremia (OR 2.175; CI 1.542-3.070), and F0-F2 fibrosis (OR 1.506; CI 1.012-2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. CONCLUSIONS A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin.

Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia

BACKGROUND In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy. PATIENTS In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations. PLT and/or fresh-frozen plasma (FFP) units were infused at the discretion of the attending physician, and the occurrence of post-procedural bleeding was related to pre-and post-infusion results. RESULTS 852 Procedures were carried out in 363 cirrhotics sub-grouped according to the Child-Pugh-Turcotte (CPT) classification (class A/B/C: 124/154/85). The infusion of PLT and/or FFP improved only marginally circulating PLT counts and INR values. Ten post-procedural bleeds occurred in the whole case series, i.e. 1 episode every 85 procedures or every 36 patients. Post-procedural bleeding was unrelated to the PLT counts, to the degree of INR abnormalities, nor to the CPT classes, but was more frequent in patients who underwent repeated investigations. In the 10 patients with the most profound alterations in PLT and/or INR values, no post-procedural bleeding occurred. CONCLUSIONS In cirrhotic patients with low PLT and/or abnormal INR values undergoing invasive investigations, post-procedural bleeding was rare and unpredicted by PLT counts or abnormal INR values. In particular, the recommendation to infuse platelets when counts are <50×103/L is not substantiated by this case series of cirrhotic patients.

Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis

It is unclear whether the efficacy and long‐term outcome of treating patients with hepatitis C virus (HCV)‐positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis.

Variation in genes encoding for interferon λ‐3 and λ‐4 in the prediction of HCV‐1 treatment‐induced viral clearance

In patients with chronic HCV‐1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ‐4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg‐interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT.

An a priori prediction model of response to peginterferon plus ribavirin dual therapy in naïve patients with genotype 1 chronic hepatitis C

BACKGROUND Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon+ribavirin therapy. METHODS In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response. The model was then validated in 423 patients (validation cohort). RESULTS In the derivation cohort, 257 achieved rapid virological response and 818 did not, with sustained virological response rates of 80.2% and 25.4%, respectively; interleukin-28B polymorphisms, fibrosis staging, gamma-glutamyl transferase, and viral load predicted sustained virological response. Assuming a <30% sustained virological response probability for not recommending Peg-interferon+ribavirin, 100 patients (25.6%) in the validation cohort were predicted a priori to fail this regimen. Assuming a ≥80% sustained virological response probability as a threshold to continue with Peg-interferon+ribavirin, 61 patients were predicted to obtain sustained virological response, and 55 of them (90.2%) eventually did. CONCLUSIONS This model uses easily determined variables for a personalized estimate of the probability of sustained virological response with Peg-interferon+ribavirin, allowing to identify patients who may benefit from conventional therapy.

Exocrine Pancreatic Insufficiency, as Assessed by Fecal Elastase-1 Levels, in Diabetic Patients: An Estimate of Prevalence in Prospective Studies

Objective: To assess the prevalence of pancreatic exocrine insufficiency (PEI) inpatients with diabetes mellitus (DM). Design: Meta-analysis of prospective, observational studies that used fecal elastase-1 estimation to determine PEI in patients with DM. Data extraction: A total of 11 studies out of 1156 retrieved references, published between 2000 and 2013, fulfilled the inclusion criteria. The primary outcome measure was proportions of patients with DM and PEI. Results: Of the 2891 patients enrolled, 921 (31.8%) showed abnormal (i.e, 100 but <200 μg/g) in elastase-1 excretion. In 921 patients with type-1 DM, the weighted rate of PEI was 37.7% (CI 27.2-49.5), and 26.2% (CI 19.4-34.3) in 1970 type-2 diabetic patients, a difference of 11.5% (p=0.09). Of patients with abnormal (<200 μg/g) fecal elastase-1 concentrations, severe PEI was present in 53.4% (CI 45.2-61.4) of type-1, and in 50.3% (CI 40.7-59.9) of type-2 diabetic patients. Limitation: Some variables, which may influence fecal elastase-1 excretion, could not be controlled due to missing data. Conclusions: When explored by fecal elastase-1 testing, one in three patients with DM showed signs of impaired exocrine function. The results suggest that testing for PEI should be part of the diagnostic work-up of patients with DM.

Hepatitis C Virus Clearance in Older Adults

To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct‐acting antiviral therapy.

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: the ITAL-C network study

The effectiveness of a 12‐week course of sofosbuvir‐ledipasvir in treatment‐experienced HCV genotype 1b‐infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post‐treatment week 12 (SVR12) of sofosbuvir‐ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir‐ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir‐ledipasvir alone for 24 weeks) consecutive HCV genotype 1b‐infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child‐Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child‐Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir‐ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir‐ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12‐week treatment with sofosbuvir‐ledipasvir alone might be suboptimal for this setting of patients.