Background Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa2b regimen and the peginterferon alfa-2a regimen. Results Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peg interferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon– ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.)

/pdf/peginterferon-alfa-2b-or-alfa-2a-with-ribavirin-for-2nk440xpf1.pdf

Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.24452

Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: A meta‐analysis

Introduction
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma.

Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis

With the widespread use of ultrasonography (US) and computerized tomography (CT), the usefulness of alpha-fetoprotein assay in the diagnosis of hepatocellular carcinoma (HCC) has decreased. The aim of our study was to evaluate the best cut-off value for serum alpha-fetoprotein to discriminate between liver cirrhosis (LC) and HCC and the factors influencing levels in a Sicilian population. Three hundred and seventy-two patients with LC and 197 with HCC-associated LC were studied. The etiology was: HCV in 288 cases (77.4%) of LC and 147 cases (75%) of HCC; HBV in 31 cases (8.3%) of LC and 15 cases (7.6%) of HCC; HCV/HBV in 21 cases (5.6%) of LC and 6 cases (3.0%) of HCC; non-viral in 32 cases (8.6%) of LC and 29 cases (15%) of HCC. Hepatic function was estimated by the Child-Pugh's score; the TNM classification was used in HCC. The area under the ROC curve was 0.81 +/- 0.02; the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was 30 ng/ml. At this level sensitivity (SE) was 65%, specificity (SP) 89%, positive predictive value (PPV) 74% and negative predictive value (NPV) 79%. When the patients were divided at this cut-off point into two groups according to viral or non-viral etiology, PPV was 70% versus 94%, respectively (p 30 ng/ml correlated positively only with the TNM stage (p < 0.0001). In conclusion, the best cut-off value for serum AFP in our study population was 30 ng/ml, but at this level sensitivity was low. This cut-off value was more useful in detecting non-viral HCC, because PPV was significantly higher than in viral HCC; therefore, our data confirm that the usefulness of AFP in the diagnosis of HCC of viral etiology is limited, being more useful in HCC of non-viral etiology.

Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.

This study was designed to assess patients with chronic hepatitis C (CHC) for the presence of thyroid autoimmunity and dysfunction, to evaluate the risk of thyroid disorders associated with interferon (IFN) therapy, and to survey the outcome of possible treatment-related thyroid injury. Out of 104 consecutive untreated patients (30 women and 74 men; mean age, 52.7 years), 8 (7.7%) were found seropositive for thyroid autoantibodies (ThyAb), whereas seropositivity in healthy controls was 1/98 (1.3%). The relative increase in risk of developing thyroid autoimmunity associated with CHC was 760% (95% Cl, 220–1300%). No patients had abnormalities of thyroid function tests, but on IFN treatment, 3/3 patients showed a rapid over-range rise in circulating thyrotropin, which returned to normal after therapy discontinuation. In the other 5 seropositive patients who refused treatment, thyroid function remained normal. Out of the 58 initially seronegative patients who consented to IFN treatment, 9 (15.5%) developed thyroid autoimmunity. Seven of them (77,7%) had thyroid dysfunction: hypothyroidism in 4 cases, transient thyrotoxicosis in 2 cases. The last patient developed TSH-receptor antibodies and Graves’ disease, requiring methimazole therapy. Thyroid function recovered in the former 6 cases following IFN discontinuation. In the 28 initially seronegative patients who refused IFN and participated in a preliminary tauroursodeoxycholic acid trial, antithyroglobulin antibodies alone appeared in one case, but no thyroid dysfunction was observed. The relative risk of thyroid autoimmune disorder associated with IFN therapy was 342% (28–636%). The patients with CHC were unlikely to develop thyroid dysfunction in the absence of IFN therapy, in spite of being ThyAb seropositive. Moreover, a considerable proportion of seronegative patients, when IFN-treated, developed thyroid autoimmunity and then thyroid dysfunction. Both in seropositive and seronegative patients immediate IFN discontinuation normalized thyroid function and hormone replacement therapy was not necessary.

Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy.

Background/Aim: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center.



Patients: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-α 2a 180 μg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al.



Results: Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (χ2=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), γ-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR.



Conclusions: This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild–moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.

S. Tripi

Papers

Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.

Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

Percutaneous Liver Biopsy: A Safe Outpatient Procedure?

Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis.