Multidisciplinary treatment of hepatocellular carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part II - Non-surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document.

Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document.

Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis.

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed.

Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice.

Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises-advanced chronic liver disease-to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC.

Status of, and strategies for improving, adherence to HCC screening and surveillance.

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide and the main cause of death in patients with cirrhosis. Secondary prevention of HCC can be accomplished through the serial application of screening tests (ultrasound with or without alpha-fetoprotein) to detect the presence of subclinical lesions amenable to potentially curative treatment, such as surgery and ablation. The efficacy of HCC screening is accepted by hepatologists in terms of decline in cancer-specific mortality, but its translation into clinical practice is less than ideal.

Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study.

Unlabelled: Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies.

External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: A multicenter cohort study.

Unlabelled: Several staging systems for hepatocellular carcinoma (HCC) have been developed. The Barcelona Clinic Liver Cancer staging system is considered the best in predicting survival, although limitations have emerged. Recently, the Italian Liver Cancer (ITA.

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity.

Objectives: We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis.

Methods: We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria.

Management and prognosis of hepatocellular carcinoma in the elderly: Results of an in-field multicenter cohort study.

Aims: This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice.

Material & Methods: From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non-elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group.

The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study.

Background & Aims: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Results: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients.

Management of hepatocellular carcinoma in the elderly.

Mean age of hepatocellular carcinoma (HCC) patients has been progressively increasing over the last decades and ageing of these patients is becoming a real challenge in every day clinical practice. Unfortunately, international guidelines on HCC management do not address this problem exhaustively and do not provide any specific recommendation. We carried out a literature search in MEDLINE database for studies reporting on epidemiology, clinical characteristics and treatment outcome of HCC in elderly patients.

Trend of improving prognosis of hepatocellular carcinoma in clinical practice: an Italian in-field experience.

Background: Recent data suggest that outcome of hepatocarcinoma is improving.

Aims: In order to explore whether survival is also increasing in clinical practice, we compared two multicenter independent in-field cohorts of cirrhotics with newly diagnosed HCCs.

Methods: Cohort 1 (C1) consisted of 327 patients enrolled between January and December 1998, and cohort 2 (C2) included 826 patients enrolled between September 2008 and November 2012.

Advanced precancerous lesions in the liver.

We will focus on precursors of the most common liver cancer, i.e. hepatocellular carcinoma (HCC), which takes place in 90% of cases in a hepatitis/cirrhotic setting.

Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma: results of an Italian field practice multicenter study.

Aim: Adherence to and the applicability of practice guidelines for the management of hepatocellular carcinoma (HCC) in field practice have not been fully addressed. We designed a multicenter field practice prospective study to evaluate the adherence to the 2005 American Association for the Study of Liver Diseases guidelines in Italy.

Materials & Methods: The study began in September 2008 and consecutively enrolled cirrhotic patients with newly diagnosed HCC from 30 local, nonreference centers in Italy.

Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance.

Background: The aetiological factors of hepatocellular carcinoma may vary over time.

Aims: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients.

Methods: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period.

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma.

Unlabelled: The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs (≤2 cm) and nonsmall HCCs by core biopsy with a 20- to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.

Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study.

Objectives: The identification of prognostic factors associated with mortality is crucial in any clinical setting.

Methods: We enrolled in a prospective study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis, consecutively observed between 1989 and 1992. At entry, patients underwent upper endoscopy to detect esophageal varices, and were then surveilled by serial clinical and ultrasonographic examination.

Hepatocellular dysplastic nodules.

The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis, that include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN) and high grade dysplastic nodules (HGDN). The latter belong to the "bordeline malignancy" cathegory requiring an accurate distinction from well-differentiated and early hepatocellular carcinoma. Nodules in cirrhosis are usually detected by non-invasive imaging techniques, being the latter unable to discriminate malignant from non-malignant forms, particularly in the 1-2 cm sized group.

Epidemiology and outcome of hepatocellular carcinoma in Lombardy.

Background And Aims: Information on the impact of therapeutic strategies of hepatocellular carcinoma is still incomplete due to the lack of surveys involving primary-care centres.

Patients And Methods: The Gruppo Epatologico Lombardo (GEL) carried out a study on 361 incident hepatocellular carcinoma observed from January to December 1998 in 22 hospitals in Lombardy. The clinical, pathological and therapeutic data were collected from all patients; 5-year survival and factors related to outcome were analysed.

Hepatocellular dysplastic nodules.

The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis, which include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN), and high grade dysplastic nodules (HGDN). The latter belong to the "bordeline malignancy" category requiring accurate distinction from well-differentiated and early hepatocellular carcinoma (HCC). Nodules in cirrhosis are usually detected by non-invasive imaging techniques, which are unable to discriminate malignant from non-malignant forms, particularly in the 1-2-cm sized group.

Daily dose of interferon alpha-2b and ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection: a randomised controlled study.

Objective: The treatment of patients with hepatitis C virus (HCV) genotype 1 infection remains disappointing.

Methods: In 1999, we started a multicentre study comparing two regimens of recombinant interferon (IFN) alpha-2b plus ribavirin. Group A (90 patients) received ribavirin plus IFN alpha-2b 5 MU/day for 1 month (induction therapy) followed by IFN alpha-2b 5 MU thrice weekly for 5 months.

Triple antiviral therapy in HCV positive patients who failed prior combination therapy.

Aim: To assess the efficacy of triple therapy (peginte-rferon or high dose standard interferon, plus ribavirin and amantadine) in nonresponders to prior combination therapy.

Methods: A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 mug/wk of peginterferon-alpha-2a (40 kDa) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group A) or interferon-alpha-2a (6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group B).

[Topical beclomethasone dipropionate (BDP) in intestinal inflammatory diseases: the results of a multicentre trial].

The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.