Immunological alterations in hepatitis C virus infection

A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus(HCV)infection,focusing the attention of physicians and researchers on the close association between HCV and immune disorders.HCV lymphotropism represents the most important step in the pathogenesis of virusrelated immunological diseases and experimental,virologic,and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases,such as rheumatoid arthritis,Sj?gren syndrome,hemolytic anemia and severe thrombocytopenia,and in organ-specific autoimmune diseases,such as autoimmune hepatitis,thyroid disorders and diabetes.This review will outline the principal aspects of such HCVinduced immunological alterations,focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

untreatable hepatocellular 癌的自然历史: 回顾的队研究

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 for each patient including all clinical,laboratory and imaging variables necessary for the outcome prediction staging systems considered.HCC staging was performed according Barcelona Clinic Liver Cancer(BCLC) and Cancer of the Liver Italian Program scores.Follow-up time was defined as the number of months from the diagnosis of HCC to death.Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival.RESULTS:Seventy-five per cent of patients had hepatitis C.Ascites was present in 169 patients(53%),while hepatic encephalopathy was present in 49 patients(15%).The Child-Pugh score was class A in 105 patients(33%),class B in 142 patients(44%),and class C in 73 patients(23%).One hundred patients(31%) had macroscopic vascular invasion and/or extrahepatic spread of the tumor.A single lesion 】 10 cm was observed in 34 patients(11%),while multinodular HCC was present in 189 patients(59%).Thirty nine patients(12%) were BCLC early(A) stage,55(17%) were BCLC intermediate(B) stage,124(39%) were BCLC advanced(C) stage,and 102(32%) were endstage BCLC(D).At the time of this analysis(July 2011),28(9%) patients were still alive.Six(2%) patients who were lost during follow-up were censored at the last visit.The overall median survival was 6.8 mo,and the 1-year survival was 32%.The 1-year survival according to BCLC classes was 100%,79%,12% and 0%,for BCLC A,B,C and D,respectively.There was a significant difference in survival between each BCLC class.The median survival of patients of BCLC stages A,B,C and D was 33,17.4,6.9,and 1.8 mo,respectively(P 【 0.05 for comparison between stages).The median survival of Child-Pugh A,B and C classes were 9.8 mo(range 6.4-13),6.1(range 4.9-7.3),and 3.7(range 1.5-6),respectively(P 【 0.05 for comparison between stages).By univariate analysis,the variables significantly associated to an increased liklihood of mortality were Eastern Cooperative Oncology Group performance status(PS),presence of ascites,low level of albumin,elevated level of bilirubin,international normalized ratio(INR) and Log-[(α fetoprotein(AFP)].At multivariate analysis,mortality was independently predicted by bad PS(P 【 0.0001),high INR values(P = 0.0001) and elevated Log-(AFP) levels(P = 0.009).CONCLUSION:This study confirms the heterogeneous behavior of untreated HCC.BCLC staging remains an important prognostic guide and may be important in decision-making for palliative treatment.

Hyperferritinemia is a risk factor for steatosis in chronic liver disease

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and γ-glutamyltransferase were independent predictors of steatosis. Ferritin levels were signifi cantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

clinical course and prognostic factors of hepatorenal syndrome:a retrospective single-center cohort study

AIM: To investigate clinical and biochemical features of hepatorenal syndrome(HRS), to assess short and long- term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients(53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and al- bumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013. RESULTS: HRS type 1 was diagnosed in 15 patients(45.5%). Hepatitis C virus infection was the primary etiology(69.6%), followed by alcohol(15.2%), and cryptogenesis(15.2%). Complete response to therapy was obtained in only 3 cases(9.1%) and partial re- sponse in 7 patients(21.2%). Median survival was 30 d(range: 10-274) without significant differences be- tween type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C(P = 0.009), presence of hepatocel- lular carcinoma(P = 0.04), low serum sodium(P = 0.02), high bilirubin values(P = 0.009) and high Model for End-stage Liver Disease(MELD) score(P = 0.03) were predictive factors of 30-d mortality. By multivari- ate analysis, only serum sodium < 132 mEq/L(OR = 31.39; P = 0.02) and MELD score > 27(OR = 18.72; P = 0.01) were independently associated with a survival of less than one month. CONCLUSION: HRS still has a poor prognosis, even when vasoactive drug therapies are extensively used.

Interferon β-1a alone or in combination with ribavirin: A randomized trial to compare efficacy and safety in chronic hepatitis C

AIM: To compare the efficacy and safety of recombinant human IFN β-1a alone or in combination with ribavirin in treatment-na(i)ve subjects with chronic hepatitis C.METHODS: Open, randomized trial was performed in 6 Italian tertiary centers: 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN β-1a subcutaneously daily for 24 wk, alone (Group 1, n = 51) or in combination with ribavirin 1 000 to 1 200 mg/d (Group 2, n = 51).RESULTS: The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 (non-significant). Twenty-four weeks after stopping therapy,sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 (non-significant). All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events.CONCLUSION: Recombinant human IFN β-1a, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis C patients who are unable to tolerate pegylated α-interferon.

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy:A randomized controlled trial

AIM: To assess the efficacy of different schedules of consensus interferon (CIFN) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy. METHODS: Forty-five patients (34 males and 11 females) with chronic hepatitis due to hepatitis C virus (HCV) genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk (group A, n = 22) or 18 μg CIFN three times per week for 52 wk (group B, n = 23) in combination with ribavirin 800 to 1200 mg daily for 52 wk (according to body weight). Virological response was evaluated at week 24 (EVR), at the end of treatment (ETR) and at 76 wk (SVR). RESULTS: By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects (mostly intolerance) in 15 patients (6 in group A and 9 in group B). IFN dose reduction was needed in 2 patients (1 in group A and 1 in group B). Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% (6 in group A and 6 in group B). CONCLUSION: CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustainedviral clearance independently of dosage of the drug. This may be due to its scarce tolerability.