Model of Care for Microelimination of Hepatitis C Virus Infection among People Who Inject Drugs.

BACKGROUND: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. AIMS: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. METHODS: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. RESULTS: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10-58.38; p = 0.005). CONCLUSION: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.

Prevalence of and risk factors for fatty liver in the general population of Northern Italy: the Bagnacavallo Study.

BACKGROUND: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. METHODS: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. RESULTS: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. CONCLUSIONS: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes.

Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An INNOVATE study protocol.

INTRODUCTION: Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set. METHODS: This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib. CONCLUSIONS: Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.

Transient elastography in healthy subjects and factors influencing liver stiffness in non-alcoholic fatty liver disease: An Italian community-based population study.

BACKGROUND: Few studies have been performed to explore parameters that influence liver stiffness measurement (LSM) using transient elastography in general population. AIM: To explore factors influencing LSM in healthy and in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: LSM was performed in a well-characterized cohort of subjects aged between 30 and 63 years. After exclusion of any causes of liver disease, the healthy cohort was defined and was compared with participants with NAFLD. The 95th percentile value of LSM in healthy was used as a cutoff suggesting relevant fibrosis. RESULTS: Among 780 subjects evaluated, 331 were defined as healthy. The median value was 4.4kPa (3.7-5.2) and the 95th percentile was 6.8kPa. LSM was not influenced by gender, age, anthropometrics and biochemical parameters. Only insulin resistance was independently associated with increasing of LSM. In the cohort of 157 subjects with NAFLD, LSM was higher than in healthy (5.6±1.9 vs 4.6±1.3kPa; p<0.001). On multivariate analysis, the degree of steatosis was independently associated with increasing of LSM in NAFLD cohort (ß=0.271; 95% CI=0.026-0.095; p<0.001). Participants with diabetes and/or severe steatosis had the highest probabilities of relevant fibrosis. CONCLUSIONS: LSM varies between 3.7 and 5.2kPa in healthy Caucasians and is influenced only by insulin resistance. In NAFLD, severe steatosis and diabetes are factors influencing LSM.

Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review.

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.

Pulmonary scintigraphy as a method to investigate gastrobronchial communication in tracheostomized patients.

Amyotrophic Lateral Sclerosis (ALS) is a degeneration of somatic motor neurons extending from upper motor cortical pyramidal neurons to lower motor neurons of the brainstem and cord. During the course of the disease patients require invasive procedures for nutrition and ventilation. Percutaneous Endoscopic Gastrostomy (PEG), performed in patients with impaired swallowing, is a safe procedure for the administration of Enteral Nutrition (EN). In the advanced stages of the disease patients develop a ventilatory failure due to muscolar weakness in these case they need a permanent tracheal tube with mechanical ventilation. Here we reported a case of a patient with Amyotrophic Lateral Sclerosis (ASL) who developed an increased gastric endocavitary pressure after a Percutaneous Endoscopic Gastrostomy (PEG).

Paraparesis induced by extramedullary haematopoiesis.

We describe a case of worsening paraparesis induced by spinal cord compression at T6-T7 levels associated with compensatory extramedullary haematopoiesis from a compound heterozygote for haemoglobin E and for ß-thalassemia. An emergency T3-T9 laminectomy was performed with excision of the masses and complete rehabilitation of the patient.

Role of contrast-enhanced ultrasonography in primary hepatic lymphoma.

OBJECTIVE: Ultrasonography is the first examination performed for screening of hepatocellular carcinoma (HCC); contrast-enhanced ultrasonography (CEUS) can help discriminate between HCC and other lesions. Primary hepatic lymphoma (PHL), even if rare, should be considered in the differential diagnosis of focal liver lesions (FLLs). Few data are available in the literature about the role of CEUS in the diagnosis of PHL; we tried to determine whether CEUS could have a role in this setting. METHODS: we describe 2 cases of primary non-Hodgkin lymphoma of the liver associated with hepatitis B virus (HBV) infection. The first patient was a 62-year-old man who was an HBV-inactive carrier, and the second was a 58-year-old man with type 2 diabetes and chronic HBV hepatitis. RESULTS: in both cases, ultrasonography showed a hypoechoic liver lesion (4 and 3 cm, respectively) with irregular margins in segment 4 of the liver. On CEUS, these lesions were inhomogeneously hyperenhanced in the arterial phase and hypoenhanced in the portal and late phases. Contrast-enhanced computed tomography (CT) in both patients showed slight hyperenhancement in the arterial phase and hypoenhancement in the remaining phases. Needle biopsy showed marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in both patients. CONCLUSIONS: Contrast-enhanced ultrasonography and CT did not help us differentiate PHL from HCC; in fact, in both cases we saw the characteristic findings of primary HCC. Primary hepatic lymphoma is a rare condition, but it should always be considered in the differential diagnosis of FLLs. We stress the important role of liver biopsy when imaging indicates HCC in patients without underlying cirrhosis.

Liver AL amyloidosis as a possible cause of high liver stiffness values.

The liver is a common site of amyloid deposition in primary systemic amyloidosis. We report the case of a 52-year-old white woman complaining of hepatomegaly, high levels of alkaline phosphatase and serum gamma-glutamyl transferase. Other laboratory tests showed proteinuria with light-chain type lambda. Color Doppler ultrasonography showed an enlarged bright liver with hepatopetal portal blood flow. Fine-needle aspiration biopsy of abdominal fat, with Congo red stain, was positive for amyloid. No liver biopsy was performed, but transient elastography showed high liver stiffness values (75 kPa), suggestive of amyloid infiltration, as other causes of elevation had been ruled out by clinical, laboratory and radiological findings. Bone marrow morphology and immunoistochemistry confirmed low-grade plasmacytoma with amyloidosis.

Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis.

Hepatitis C virus (HCV) infection affects about 3% of the world's population and often leads to chronic liver disease. In some industrialized countries, HCV prevalence increases with age, but the optimal management of older patients has not been accurately defined. HCV infection can also lead to lymphoproliferative disorders, the most common being mixed cryoglobulinemia (MC), and also for this condition that frequently affects elderly patients, the optimal therapeutic strategy is still debated. We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines. The patient underwent a treatment with interferon and ribavirin. Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms. After the end of treatment, HCV replication relapsed, but cryoglobulinemia and cutaneous symptoms did not recur. In the absence of definite treatment guidelines in this particular context, our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

Aberrant Notch3 and Notch4 expression in human hepatocellular carcinoma.

BACKGROUND: Notch signalling is altered in several solid tumours and it plays a role in growth inhibition and apoptosis of hepatocellular carcinoma (HCC)-derived cell lines, bile duct development and hepatocyte regeneration. AIMS: This study aims to analyse the expression of Notch3, Notch4 and HES1 and HES6 as Notch-target genes in HCC, matched non-neoplastic tissue and HEPG2 cells. RESULTS: Notch3 and Notch4 are not expressed in normal liver and in chronic hepatitis surrounding HCC. Cirrhotic tissue stains negative for Notch3, while Notch4 is expressed by hepatocytes at the edge of regenerative nodules and in cell planes adjacent to fibrous septa. HCC tissue displays Notch3 and Notch4 abnormal accumulation, respectively, in 78% and 68% of the cases. The endothelium of hepatic veins with neoplastic permeation is frequently Notch4 positive. An upregulation of Notch3 mRNA was found in 95% of HCCs vs cirrhosis (P=0.0001), while Notch4 mRNA was downregulated in 80% of HCCs. HES6 mRNA expression was higher in HCC tissue when compared with cirrhosis (P=0.007), paralleling Notch3 mRNA expression. The HEPG2 cell line displays high Notch3 and low Notch4 protein and mRNA levels. CONCLUSIONS: These descriptive findings suggest an aberrant expression of Notch3 and Notch4 in HCC and allow the hypothesis of an activation of Notch signalling by Notch3.