Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: personal experience and review of the literature.

Bisphosphonates (BPs) are a class of synthetic drugs commonly used to treat bone metastasis and various bone diseases that cause osseous fragility (such as osteoporosis). Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common complication in patients who received BPs, especially intravenously. Recently, osteonecrosis of the jaw (ONJ) caused by chemotherapeutic not belonging to BPs drug class has been reported. For this reason, it has been proposed recently to rename BRONJ in antiresorptive agents related osteonecrosis of the jaw (ARONJ), to include a wider spectrum of drugs that may cause osteonecrosis of the jaw. The most debated topic about ARONJ/BRONJ is therapy. The most adequate procedure is far from being standardized and prevention seems to play a pivotal role. In our study, we considered 72 patients with BRONJ with nonsurgical therapy, surgical therapy, and surgical therapy with platelet rich plasma (PRP) gel to evaluate its therapeutic effect in promoting ONJ wounds healing. Good results showed by PRP in improving wound healing give away to case-control randomized studies that could give definitive evidence of its effectiveness.

Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver transplantation: an open single-arm prospective study.

Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long-term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to SC self-injection after a single training. The treatment was effective in maintaining trough anti-HBs levels >100 IU/L. No severe drug-related side effects occurred. Fifteen injection-site small hematomas and four cases of mild itch occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566 IU/L) and 97.8% of patients had an anti-HBs level >150 IU/L. Due to high mean level of anti-HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long-term prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti-HBs levels.

Endovascular treatment of femoropopliteal stenoses/occlusions with a SilverHawk directional atherectomy device: immediate results and 12-month follow-up.

PURPOSE: This paper reports our immediate and 12-month follow-up results in the treatment of arterial stenoses/occlusions of the femoropopliteal region with the use of the SilverHawk directional atherectomy device (EV3, USA). MATERIALS AND METHODS: In an 18-month period, we treated 18 patients (13 men, five women, age range 39-81 years) with the SilverHawk directional atherectomy device. Inclusion criteria were symptomatic femoropopliteal stenosis/insufficiency, nonresponsiveness to medical therapy, and Rutherford categories 3-5. Exclusion criteria were based on the preliminary colour Doppler ultrasound (US) assessment and were plaque with a calcified component >50% and inadequate upstream and/or downstream vascular bed. Patients with severe vascular impairment, classified as TransAtlantic Inter-Society Consensus (TASC) D, were also excluded. RESULTS: The procedure was successfully completed in all cases, with evident recanalisation and sufficient wall remodelling. No major complication was observed. At assessment immediately after the procedure and over the following days, an improvement in clinical symptoms and in the Rutherford scale was observed. Follow-up at 2 and 12 months identified one case of distal reocclusion subsequently treated with amputation, and two cases of restenosis (primary patency 79%) successfully treated with a repeat procedure (secondary patency 96%). CONCLUSIONS: The SilverHawk directional atherectomy device proved to be an effective and safe tool in all our patients treated for femoropopliteal stenosis/occlusion, with a significant improvement in both imaging findings and clinical signs and symptoms.

Human fibroblasts and 900 MHz radiofrequency radiation: evaluation of DNA damage after exposure and co-exposure to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)-furanone (MX).

The aim of this study was to investigate DNA damage in human dermal fibroblasts from a healthy subject and from a subject affected by Turner's syndrome that were exposed for 24 h to radiofrequency (RF) radiation at 900 MHz. The RF-radiation exposure was carried out alone or in combination with 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a well-known environmental mutagen and carcinogen produced during the chlorination of drinking water. Turner's syndrome fibroblasts were also exposed for a shorter time (1 h). A signal similar to that emitted by Global System for Mobile Communications (GSM) mobile phones was used at a specific absorption rate of 1 W/kg under strictly controlled conditions of temperature and dosimetry. To evaluate DNA damage after RF-radiation exposure alone, the alkaline comet assay and the cytokinesis-block micronucleus assay were used. In the combined-exposure experiments, MX was given at a concentration of 25 microM for 1 h immediately after the RF-radiation exposure, and the effects were evaluated by the alkaline comet assay. The results revealed no genotoxic and cytotoxic effects from RF radiation alone in either cell line. As expected, MX treatment induced an increase in DNA migration in the comet assay, but no enhancement of the MX-induced DNA damage was observed in the cells exposed to RF radiation.

Elevated CD4+/CD25+ T-cell frequency and function during hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIM: Factors involved in hepatitis C virus (HCV) recurrence versus acute cellular rejection are not fully understood. The aim of the present study was to investigate whether patients with recurrence after liver transplantation (OLT) showed similar CD4(+)/CD25(+) cell frequency and function as those who became chronically infected. PATIENTS AND METHODS: After written informed consent, we enrolled 20 patients (group A) who underwent OLT with HCV recurrence within 6 months. HCV-RNA and hypertransaminasemia were used to assess the reactivation of viral hepatitis. CD4(+)/CD25(+) T cells were enumerated using a flow cytometry assay, gated on CD3 cells, stained for FoxP3. After immunomagnetic sorting (Dynal, Oslo, NW), Treg suppressor activity was measured, as the ability to inhibit proliferation of autologous CD4(+)/CD25(-) T cells (anti-CD3/CD28 stimulation-1:2, 1:20 ratio). Eight patients with acute hepatitis C who evolved to a chronic infection after 6 months (group B) were used as positive controls, while 10 healthy individuals were negative controls (group C). RESULTS: We did not observe any difference in CD4(+)/CD25(+) frequency or function among group A compared with group B (CD4(+)/CD25(+) = 14% +/- 2% versus CD4(+)/CD25(+) = 16% +/- 3%), although both groups were significantly increased with respect to group A (CD4(+)/CD25(+) = 6% +/- 3%; Mann-Whitney U test, P < .01). CONCLUSION: Patients developing HCV recurrence after OLT have the same immunoregulatory network as patients with acute hepatitis C evolving to persistent infection, likely suggesting that CD4(+)/CD25(+) numbers may be a marker to predict recurrence of HCV after OLT.

The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer.

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.

Evidence of liver histological alterations in apparently healthy individuals evaluated for living donor liver transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) represents an important therapeutic option for patients with end-stage liver disease (ESLD). It has been reported that steatosis may be a serious problem in patients who donate a part of their liver. Liver biopsy represents an accepted method to assess the rate of steatosis and the possible risk to the donor. Nonetheless, some histological abnormalities have been documented in the specimens from potential donors. The aim of this study was to evaluate the possible hepatic histological alterations among apparently healthy candidates for liver donation who did not show serological or ultrasound (US) evidence. MATERIALS AND METHODS: From January 1, 2005 until October 15, 2006, we performed virological, biochemical, and tumor marker evaluations and liver biopsies on 20 LDLT donor candidates. At histological evaluation we classified the evidence of steatosis (5%-10% or 10%-20%), fibrosis (absent or 1-3 portal space), inflammation, iron deposition, biliary neoductulation, and portal vein vascular alterations. RESULTS: Among the 20 subjects, serological markers did not show any pathological alterations. At liver biopsy we found: steatosis (5%-10%) in 6 individuals (about 30%) with 1 ranging from 10% to 20%; iron deposition in 4 (20%); biliary neoductulation in 3 (about 16%); fibrosis in 4 (20%); inflammation in 5 (25%); and portal vein dilatation in 10 (50%). CONCLUSIONS: Our data showed that apparently healthy individuals who did not display serological markers or US evidence of pathology had liver histological abnormalities. This result suggested that in absence of clinical or laboratory alterations, liver biopsy may represent a useful diagnostic tool for living donor candidates. Long-term follow-up results for the laboratory data among those patients should be performed even though they were not qualified for LDLT.

Multiparameter characterisation of vertebral osteoporosis with 3-T MR.

PURPOSE: This study was undertaken to evaluate the diagnostic capabilities of 3-Tesla (T) magnetic resonance (MR) in vertebral osteoporosis. MATERIALS AND METHODS: Thirty subjects (ten healthy controls, ten with osteoporosis but no fracture, ten with osteoporotic vertebral fractures) underwent MR of the lumbar spine. Turbo spin echo (TSE) T1-, T2- and T2- spectral selection attenuated inversion recovery (SPAIR) weighted imaging and spectroscopy for the selective evaluation of water and fat content were performed. The apparent diffusion coefficient (ADC) was calculated, and diffusion tensor imaging (DTI) was performed to create a map of the spatial arrangement of the tissue structures. RESULTS: Morphological imaging detected recent vertebral fractures. In osteoporotic patients, spectroscopic imaging demonstrated an increase in the saturated fats and a decrease in the ADC, whereas the data provided by DTI demonstrated a bone structure with medium-degree anisotropy. DISCUSSION: Osteoporosis is characterised by trabecular thinning, with an increase in the intertrabecular spaces, which are filled with fats. The anisotropic study and the subsequent assessment of colour and vector maps can provide a noninvasive tool for assessing the risk of fracture due to osteoporosis.

Acute rejection after liver transplantation: Is there a specific immunological pattern?

The aim of the study was to assess various T-cell subsets and cytokine secretion patterns both in liver tissue and in the peripheral blood of 24 liver transplant patients to assess possible specific immunological involvement in early acute rejection episodes after liver transplantation. Particularly, we studied CD4+ CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine possible Th1-like immune responses and the immunomodulation expressed by Treg cells in acute liver rejection, respectively. As a control group we included patients transplanted without acute rejection. Early acute rejection within the first 4 weeks was proven histologically in 42% of patients. It was associated with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells was evident in patients with acute rejection (P < .001). Our data suggested that a preferential Th1-like immune mechanism operated in local fashion as characterized by a decreased presence in the liver and blood of Treg cells.

Multidetector CT and dentascan software: dosimetric evaluation and technique improvement.

PURPOSE: The development of new operative techniques in oral and maxillofacial surgery within the last few years has led to an increasing demand for Dentascan examination, also in paediatric patients. It is necessary to modify acquisition parameters to reduce the absorbed dose. The aim of this study was to define a Dentascan protocol in which a reduced X-ray dose could be used. MATERIALS AND METHODS: Dosimeters were applied to the eyes, mouth, parotid glands, thyroid and back of the neck of an anthropomorphic Plexiglas phantom that underwent multidetector computed tomography (MDCT) Dentascan examinations. Both 120kV and 80 kV were used to study the mandibular and maxillary arches. RESULTS: Examinations obtained with the 80 kV protocol showed a ten-fold reduction in the absorbed dose, without affecting image quality. CONCLUSIONS: We suggest a Dentascan protocol that reduces the X-ray dose administered to the patient while ensuring the same high diagnostic accuracy.

Endoscopic management of foreign bodies in the upper gastrointestinal tract: report on a series of 414 adult patients.

BACKGROUND AND STUDY AIMS: Ingestion of foreign bodies is a common occurrence. Few papers in the literature report experience and outcome at tertiary centers. The aim of this paper is to report the management and the outcomes in 414 patients admitted for suspected ingestion of foreign body between May 1995 and December 1999. METHODS: A plain radiographic film of the neck, chest or abdomen was obtained in the case of radiopaque objects, and in order to rule out suspected perforation: in such cases a computed tomography (CT) study was also performed. All patients were asked to give their informed consent, which was refused by three patients. Anesthesia was always used, either conscious sedation (86.8 %), or general anesthesia in the case of poor patient tolerance (13.2 %). All patients underwent an endoscopic procedure within six hours of admission. A flexible scope was used in all patients and a wide range of endoscopic devices was employed. RESULTS: Foreign bodies were found in 64.5 % of our patients. Almost all were found in the esophagus. The types of foreign body were very different, but they were chiefly food boluses, bones or cartilages, dental prostheses or fish bones. In three patients (1.1 %) it was impossible to endoscopically remove the foreign body, which was located in the cervical esophagus: all these three patients required surgery. No complications relating to the endoscopic procedure were observed, but 30.7 % of patients had an underlying esophageal disease, such as a stricture. Only eight patients required a second endoscopic procedure, performed by a more experienced endoscopist. CONCLUSION: Foreign body ingestion represents a frequent reason for emergency endoscopy. The endoscopic procedure is a successful technique which allows the removal of the foreign bodies in almost all cases without significant complications. Surgery is rarely required.

Efficacy of high dose of recombinant alpha 2b interferon on long term response in chronic hepatitis C and cirrhosis: prospective randomized multicentre study.

BACKGROUND/AIMS: The long-term response to alpha-Interferon in HCV-related chronic liver diseases is disappointing. A randomized controlled trial was conducted to investigate: 1) if doubling the standard regimen of 3 MU recombinant alpha 2b-interferon thrice weekly for one year could improve the long-term response, and 2) the efficacy of these two schedules in cirrhotic patients. PATIENTS AND METHODS: A series of 80 anti-HCV positive patients with biopsy proven liver disease (52 chronic hepatitis and 28 cirrhosis) were randomized to receive either 3 MU or 6 MU alpha 2b-interferon. RESULTS: Based on "intention-to-treat analysis", 38% in the 3 MU group and 53% in the 6 MU group had end-of-treatment response. After 24 months, 18% had long-term response: 5% in 3 MU group and 30% in 6 MU group (p < 0.008). HCV genotype had no influence on the response rate. Thirty-eight percent of the cirrhotics treated with 6 MU had long-term response, while none of those treated with 3 MU had long-term response (difference 38%; 95% confidence internal 10%-67%; p = 0.03). At the end of treatment, 38% of patients lost HCV-RNA. After 24 months only 19% remained HCV-RNA negative: 12 patients (31%) in the 6 MU group and 2 (6%) in the 3 MU group (p < 0.05). CONCLUSIONS: 6 MU of alpha 2b-interferon thrice weekly for 12 months is significantly better than 3 MU in inducing a long-term response and permanent loss of HCV-RNA. This result is particularly striking in the subgroup of cirrhotics.

Resistance to alpha interferon therapy in HCV chronic liver disease: role of hepatic fibrosis.

The response rate to interferon in HCV chronic liver disease is insufficient to date and the causes of this failure are not fully understood. Hepatic fibrosis hinders the blood-hepatocyte exchange of substances and we hypothesized that this process may also reduce the efficacy of interferon. Serum levels of connective tissue metabolites are related, to some extent, to the amount of extracellular matrix in the liver. Therefore, the usefulness was evaluated of serum tests of connective tissue metabolism compared to standard biochemical and histological parameters in predicting the probability of primary response to interferon. Sixty-eight patients with HCV chronic liver disease were treated with alpha-interferon for 1 year. At multivariate analysis time 0, the serum level of the P1 fragment of laminin was found to be the only factor independently associated with the response to treatment. As is well known, higher serum concentrations of the P1 fragment of laminin are associated with active basement membrane turnover and derangement of the hepatic structure. Therefore, this process seems to reduce the probability of response to interferon and, if confirmed, evaluation of serum the P1 fragment of laminin may be a useful test to predict the response to interferon and to define the therapeutic strategy, especially as far as the dose of interferon is concerned.