Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.

BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response.

Background: Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. Aim: To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. Methods: A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. Results: The overall survival rates …

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

Abstract Due to error-prone RNA polymerase and the lack of proofreading mechanisms, to the spread worldwide and probable long-term presence in human population, HCV showed a high degree of inter- and intra-subtype genetic variability. Protease inhibitors (PIs), a new class of drugs, have been designed specifically on the HCV genotype 1 NS3 protease three-dimensional structure. The viral genetic barrier limits the efficacy of PIs, and fourteen loci in the HCV NS3 gene are involved in resistance to PIs. A sensitive method (15 UI/ml) for study the HCV genetic profile of 125 strains from patients naive to PIs, was developed through the use of new degenerate primers for subtype 1b. We observed t…

Combination therapy with amantadine and interferon in naı̈ve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials

Abstract Background/Aims In chronic hepatitis C, clinical trials evaluating the efficacy of amantadine (AMA) and interferon (INF) compared to INF monotherapy, have produced conflicting results. We performed a meta-analysis of the individual patient's data from previous studies. Methods Nine hundred and seventy-two patients from six European centres were evaluated by means of individual patient meta-analysis, using mixed models with centres and the centre–treatment interaction fitted as random variables. Results At the end of therapy, virological responses were 38.5% (95% CI 34.1–42.8) after INF and AMA, and 29.5% (95% CI 25.5–33.6) after INF alone (P=0.003). Sustained response occurred in 1…

Time course of insulin resistance during antiviral therapy in non-diabetic, non-cirrhotic patients with genotype 1 HCV infection

Background Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance seems to improve insulin sensitivity. We aimed to evaluate the time course of IR in response to antiviral therapy in non-diabetic, non-cirrhotic G1 HCV patients and to assess the effect of metabolic factors on sustained virological response (SVR). Methods A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was >2.7. All cases had a liver biopsy scored for staging, grading and steatosis. A…

Chronic hepatitis B: who to treat and which choice of treatment?

The goal of antiviral therapy in patients with chronic hepatitis B is to prevent, through persistent suppression of HBV replication, cirrhosis and hepatocellular carcinoma. Currently, seven drugs are available: IFN-alpha, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. The choice of the drugs should always take into consideration the clinical features of patients, the antiviral efficacy of each drug, the risk of developing resistance, the long-term safety profile, the method of administration and the cost of therapy. Ideal candidates for treatment are hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis …

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…

Adefovir for lamivudine resistant HBV: More than meets the eye

– In patients with LAM resistance and high levels of HBV-DNA, especially if HBeAg positive, it may be difficult to obtain a strong virological suppression with ADV. – Restrictive criteria are needed to define virological response (HBV-DNA < 10 3 copies/ml or 200 IU/ml). – Early finding of non-response or of suboptimal response after 9–12 months of ADV therapy suggests a high risk of emergence of ADV-resistant strains and should prompt a change of treatment strategy. In patients with cirrhosis, due to the risk of liver failure, treatment changes should be considered even earlier, at 3–6 months.

Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study

Abstract AIM: To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. METHODS: From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected…

Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial

We assessed the effectiveness and safety of an induction dose of peginterferon alfa-2b (PEG-IFN) plus ribavirin for initial treatment of patients with genotype 1 chronic HCV infection in a randomized, controlled, multicenter trial.Three hundred and eleven naïve patients infected with genotype 1 and chronic hepatitis were randomly assigned to 48-week treatment with PEG-IFN once weekly (80-100 micrograms depending on body weight for 8 weeks, followed by 50 micrograms for the next 40 weeks), or standard interferon alfa-2b (IFN) 6 million units on alternate days, both in combination with ribavirin (1000-1200 mg/day).PEG-IFN plus ribavirin significantly increased sustained virological response (…

Hepatocellular Carcinoma Presenting at Contrast-Enhanced Multi–Detector-Row Computed Tomography or Gadolinium-Enhanced Magnetic Resonance Imaging as a Small (≤2 cm), Indeterminate Nodule

OBJECTIVE: The objective of the study was to measure growth rate and to determine the optimal interval time for imaging follow-up of hepatocellular carcinomas (HCCs) presenting at multi-detector-row computed tomography (MDCT) or magnetic resonance imaging (MRI) as small, indeterminate lesions. METHODS: We included patients with cirrhosis with HCC initially presenting as indeterminate lesion of 2 cm or less at MDCT or MRI August 2005 to August 2009 and with available imaging follow-up. Measures of tumor growth included tumor volume doubling time (TVDT), tumor percentual diameter increase, and tumor percentual volume increase. RESULTS: We examined 48 patients (mean age, 64 years) with 69 HCCs…

Hepatitis B: Prognosis and Treatment

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

Abstract Background/Aims HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. Methods HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy ( T 1) and at follow-up ( T 18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. Results No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load d…

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

none 29 no 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 8…

TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C

Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosi…

Comparison of Histochemical Staining Methods and Correlation with Transient Elastography in Acute Hepatitis.

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To compare Masson's trichrome (MT), Sirius red (SR) and orcein staining in acute hepatitis (AH) and to correlate them with&lt;b&gt; &lt;/b&gt;transient elastography (TE),&lt;b&gt; &lt;/b&gt;a noninvasive method to assess hepatic fibrosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We evaluated liver stiffness by TE in a cohort of 34 consecutive patients and assessed MT-, SR- and orcein-stained biopsies using the METAVIR scoring system and digital image analysis (DIA). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; MT and SR both showed severe fibrosis (stage III-IV, DIA = 12.7%). Orcein showed absent or mild fibrosis (stage 0-II, DIA = 4.…

Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIMS: Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C-->T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. METHODS: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. RESULTS: At multivariate logistic regression an…

HCV Clearance Among Hemophiliacs and Beta-Thalassemics

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases.

Abstract Background/Aim Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined. Methods We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepa…