Ultrasound-guided percutaneous thermal ablation has gained popularity as treatment for malignant hepatic tumors. It was first introduced as ablation therapy for hepatocellular carcinoma and cirrhosis comorbidity. Recently, this technique has also been used in the treatment of intrahepatic cholangiocarcinoma for patients who are not eligible for surgical resection. There are several types of thermal ablation techniques. Radiofrequency ablation and microwave ablation are two common methods that induce necrosis of the lesions. Irreversible electroporation is a relatively new non-thermal technique and is suitable in cases where thermal ablation would be ineffective or dangerous (e.g., malignant tumors close to vascular or biliary structures). Irreversible electroporation can induce tumoral necrosis without damage to vascular and biliary structures. The aim of this minireview was to describe the safety, efficacy, and clinical indications of these techniques in the treatment of patients with intrahepatic cholangiocarcinoma who are ineligible for surgery.
This manuscript is based on a recent study by Pillay et al that was published in recently. Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin. The incidence rate in Europe is lower than in developing countries, but it is a major complication with high morbidity, particularly in immunocompromised patients. They are most frequently caused by Enterobacterales infections, but hypervirulent Klebsiella strains are an emerging problem in Western countries. Amoebiasis has been a public health problem in Europe, primarily imported from other endemic foci. At the same time, this infection is becoming an emerging disease, as the number of infected patients who have not traveled to endemic areas is rising. Treatment options for hydatid liver cyst include chemotherapy, open or laparoscopic surgery, percutaneous treatment (percutaneous aspiration, re-aspiration and injection and its modification) and ''wait and watch'' strategy. Most hydatid liver cyst patients in Pillay et al's study received surgical treatment, but several studies have confirmed the safety and efficacy of percutaneous aspiration, re-aspiration and injection.
Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound (CEUS) has significantly improved the characterization of nodules first identified on conventional US. Yet, when CEUS is performed using sulfur hexafluoride (SonoVue)-the only contrast agent available in Western countries-assessment remains restricted to a single nodule per examination, and enhanced CT or MRI is still required for full characterization and staging. In clinical settings, such as hepatology, internal medicine, infectious diseases, and surgery, CEUS offers the advantage of immediate availability, enabling rapid characterization of suspicious nodules in cirrhotic livers and facilitating timely therapeutic decisions. Although the introduction of direct-acting antivirals (DAAs) has substantially reduced HCV-related HCC, HCC incidence is increasingly driven by metabolic dysfunction-associated steatohepatitis (MASH). Evidence on surveillance strategies for MASH patients remains limited, and current EASL guidelines recommend monitoring only patients with >F2 fibrosis. Additionally, the effectiveness of US in obese or diabetic/obese populations is under ongoing investigation; abbreviated non-contrast MRI has been proposed as an alternative surveillance tool, but its adoption would entail significant economic implications for healthcare systems. HCC arising from MASH-sometimes even without cirrhosis-exhibits different sonographic and pathological features. Instead of small, hypoechoic nodules, typically seen in HCV-related cirrhosis, clinicians increasingly encounter larger or multiple lesions, often accompanied by macrovascular invasion, limiting access to curative treatments. Furthermore, typical CEUS LI-RADS patterns are less frequently observed. This review summarizes the evolving US findings in the era of MASH-related HCC and underscores the continued importance of US as the primary imaging tool in routine clinical practice.
This manuscript is based on a case reported by Song et al published in the World Journal of Clinical Cases . Several challenges remain in the field of hepatocellular carcinoma (HCC) conversion therapy. Consequently, only a limited number of patients with HCC accompanied by portal vein tumor thrombosis (PVTT) and hepatic vein tumor thrombosis (HVTT) are eligible for resection. This clinical case demonstrates that considering the complexity of the disease, a multimodal and multidisciplinary approach is essential for managing HCC accompanied by PVTT and HVTT. However, the outcomes of such surgeries remain controversial. In conclusion, research on HCC conversion therapy is extremely useful for improving treatment strategies for intermediate and advanced HCC, which currently have disappointing clinical outcomes.
Liver and heart are anatomically and patho-physiologically related. In heart failure (HF) the increased right atrial pressure and volume overload cause histological changes in hepatocytes, leading to a condition known as "congestive hepatopathy" (CH), with consequent variations in liver functioning and ultrasound (US) findings. CH has specifical US findings especially regarding venous vessels aspect, easily detecting by gray-scale study, but many others can be distinguished by Doppler analysis. Usually, hepatic veins look enlarged and hypocollassing, together with signs of portal hypertension (hepatomegaly, ascites, splenomegaly, porto-systemic collaterals). Typically, in CH Doppler findings regard alterations in venous vessel flow and arterial resistance (venous system hyperpulsatility, reduced velocity flow, high resistance index in hepatic arterial Doppler spectrum). Sometimes CH and other primary hepatopathy can coexist, and therefore some of the expected variations may not manifest: it allows suspecting an unknown underlying liver disease. At last, US technologies of more recent applications, even if not routinely used, allow investigating additional aspects such as elastography that detects changes in liver elasticity or contrastographic US, able to show differences in hepatic venous opacification. However, most of these US signs are not pathognomonic, and therefore a multidisciplinary clinical reasoning must not be lacking. The aim of the present review is to easily provide US signs of liver alterations in HF, in particular right heart failure with volume overload, suggesting including liver US in instrumental diagnosis and therapeutic monitoring of HF.
Background and Aims: Patients with liver cirrhosis (LC) often have malnutrition (MN), which can be associated with decompensation, infection, and death. The aims were to determine: the prevalence of MN in patients with LC and ascites, its impact on mortality, and the relationship between MN and spontaneous bacterial peritonitis (SBP). Methods: Nutritional status (NS) was analysed in cirrhotic patients, experiencing their first episode of ascites, who were consecutively admitted at two clinical liver centres between November 2014 and October 2016. The participants underwent diagnostic paracentesis and were followed up to assess their outcomes. Results: 110 participants underwent NS assessment in addition to routine clinical procedures. The prevalence of MN was 30.9% according to corrected body mass index, 67.3% according to upper mid-arm muscle area (UMA) and 40% according to upper mid-arm fat area (UFA). The percentages of the participants remaining alive were 68.1% at 3 months, 59.3% at 6 months, 45.1% at 12 months and 24.2% at the end of the study. Univariate analysis showed that SBP, model for end-stage liver disease (MELD), UFA, UMA and age were significantly associated with mortality. Multivariate analysis showed that only SBP, MELD and UFA (hazard ratio 2.2) were independently associated with mortality. There was a correlation between adipopenia, but not sarcopenia, and SBP. Conclusions: Adipopenia, as assessed by UFA, was present in 40% of the cirrhotic patients, and it was independently associated with mortality.
INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P< 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P< 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.
Although hydatid liver cyst (HLC) is a benign disease, treatment is recommended to avoid life-threatening complications. There are several treatment options for HLC: “wait-and-watch,” medical or surgical or percutaneous treatment. The purpose of this study was to assess the long-term effectiveness of an alternative of the traditional percutaneous PAIR procedure, called double percutaneous aspiration and ethanol injection (D-PAI). This prospective, non-randomized study was conducted from 1988 to 2019 using DPAI procedure characterized by no reaspiration of the ethanol injected to replace the aspirated fluid and repetition of the procedure after 3–7 days. Two hundred and three patients with 290 HLCs underwent D-PAI. Two hundred and two HLC (160 patients) were univesicular cysts and 88 (43 patient) were multivesicular. Seventeen patients underwent one D-PAI session, 15 patients two sessions, and 18 up to four sessions. The follow-up ranged 0.9–21 years (median 6.5 years). On ultrasound, 188 cysts (64.8%) disappeared; 57 cysts (19.7%) became solid (inactive) and 45 (15.5%) showed a small inactive residual component. Parasitologic cure was very high. The overall response to D-PAI was higher than 90% considering also the procedures carried out after the first D-PAI at the time of recurrence. One patient died for anaphylactic shock. The hospital stay ranged 1–3 days. Smaller cysts (< 5 cm) healed sooner than larger cysts (p < 0.001). Long-term analysis showed that D-PAI is a safe and effective option in percutaneous treatment of viable HLC, except for CE2/CE3b in which the recurrences can be observed. This inexpensive and simple procedure can be applied everywhere and especially in developing countries.
Background . Chronic liver diseases (CHDs) are an important public health issue. The presence of significant fibrosis is a hallmark for liver disease staging and prognosis. Aims . To develop a non-invasive score that can discriminate between patients with or without fibrosis in the aim to avoid liver biopsy. Methods . Forty patients with CHDs who received liver biopsy to stage fibrosis and 12 normal subjects performed also share wave elastography (SWE) and ELF-test. We chose two different outcome for histological fibrosis (F0-F1 vs F2-F4) and (F0-F2 vs F3-F4). ELF-test and SWE were independent predictors, categorized using ROC analysis. Two scores called SCORE1 and SCORE2 were devised. Results . The discriminatory values for SCORE1 were SWE>5.62 kPa and ELF-test >9.33 and for SCORE2 were SWE>7.04 kPa and ELF-test 9.33. SCORE1 specificity was 91.7% (CI 77.5-98.2%), significatively greater than obtained using SWE 63.9% (CI 46.2-79.2%; p=0.0013) or ELF-test 83.3% (CI 67.2-93.6%; p=0.1760) separately. SCORE2 specificity was 95.2% (CI 83.8-99.4%). This value was not-significatively greater than obtained using SWE or ELF-test 81.0% (CI 65.9-91.4%; p=0.0921) separately. Conclusion . SWE and ELF-test can be performed for non-invasive staging of liver fibrosis. Their use grouped in a single score increase the specificity for the prediction of histological fibrosis stage.
With a recent randomized prospective trial revealing that thermal ablative therapy as local tumor control improved overall survival (OS) in patients with unresectable colorectal cancer liver metastases (CRLM), thermal ablation continues to remain as an important treatment option in this patient population. Our aim of this article is to review the current role of the ablative therapy in the management of CRLM patients. Main indications for thermal ablation include (I) unresectable liver lesions; (II) in combination with hepatectomy; (III) in patients with significant medical comorbidities or poor performance status (PS); (IV) a small (<3 cm) solitary lesion, which would otherwise necessitate a major liver resection; and (V) patient preference. There are several approaches and modalities for ablative therapy, including open, percutaneous, and laparoscopic approaches, as well as radiofrequency ablation (RFA) and microwave ablation (MWA). Each approach and ablation modality have its own pros and cons. Percutaneous and laparoscopic approaches are preferred due to minimally invasive nature, yet laparoscopic approach has more benefits from thorough intraoperative ultrasound (US) exam as well as complete peritoneal staging with laparoscopy. Similarly, whereas high local tumor failure rate has been a major concern with RFA, MWA or microwave thermosphere ablation (MTA) have demonstrated significantly improved local tumor control due to homogenous tissue heating, ability to reach higher tissue temperatures, and less susceptible to the "heat-sink" effect. Although liver resection is the standard of care for CRLM, there have been some retrospective studies demonstrating similar oncological outcome between ablative therapy and surgical resection in very selected populations with small (<3 cm) solitary CRLM. Lastly, ablative therapy and liver resection should not be mutually exclusive, especially in the management of bilobar liver metastases. Concomitant ablative therapy with hepatectomy may spare the patients from having two-stage hepatectomy with less morbidity. The role of the thermal ablation will continue to evolve in patients with resectable and ablatable lesions owing to newly emerging technology, in addition to new systemic treatment options, including immunotherapy for metastatic colorectal cancer (CRC).
Ultrasound (US) plays a pivotal role in the recognition of hepatocellular carcinoma (HCC) in cirrhosis (1). HCC represents the sixth most common malignancy and the fourth most frequent cause of cancer-related death in the world (2). Since the early 1980s, the US has described the fundamental findings of the HCC nodules appearing in a cirrhotic liver and significantly contributed to the knowledge of the natural history of this malignancy (3).
An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455–13.169). Our data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.
Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014).
To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years.
Background & Aims: Cirrhosis (LC) and hepatocellular carcinoma (HCC) are highly prevalent in Europe, with accompanying high mortality rates and social costs. As epidemiological data on these diseases are scarce, age-standardized death rate (ASDR) can serve as an indirect assessment of their burden.Methods: We analysed the ASDRs for LC and HCC from data reported in the WHO official death registries from 1970 to 2010, and compared ASDRs over the decades. The European Detailed Mortality Database was also used as source of data.Results: In 1970, Portugal had the highest reported mortality for LC, followed by France and Italy. However, in 2010, Finland, Austria and Germany were respectively the three highest, while the UK showed the highest increase over those four decades (+284.8%). The annual ASDRs for LC have dropped in Europe from 20.4/10(5) inhabitants in 1970 to 9.6 in 2010; a 53% decrease. For HCC, Spain, Italy and Denmark were ranked first through third, while in 2010 Italy, France and Luxembourg replaced them. Portugal had the highest increase (+654.7%). In 1980-2010, the ASDR for HCC in Europe increased from 3.4/10(5) inhabitants to 6.3, up 85.4%. In the majority of nations-except for the UK, Finland and Ireland-there was a decrease in LC mortality and an increase for HCC mortality.Conclusions: The LC mortality rate is decreasing in Europe, yet there is a significant increase in HCC mortality. This phenomenon requires greater attention so we can understand the risk factors and implement preventive measures.
The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades.To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies.A cross-sectional study involving 16 referral centres scattered all over the country in 2014.Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geographical area of residence. The presence of liver cirrhosis was diagnosed in 52.4% of cases. In comparison to previous studies, a further shift towards the oldest age groups and an increasing proportion of subjects having liver cirrhosis among all anti-delta-positive subjects are observed.Currently, hepatitis delta infection mostly affects old people who have an advanced but indolent liver disease, reflecting a survival effect. The defective hepatitis delta virus is near to disappear in the country, where it has been discovered in the second half of 70s.
Background The last Italian prevalence survey on chronic hepatitis (CH) conducted in 2001 showed that the hepatitis C virus (HCV) was the main agent associated with CH. Aim The aim of this study was to evaluate epidemiological changes in CH occurring after 13 years. Patients and methods Enrollment of 1392 CH consecutive patients referred to 16 Italian liver units in 2014 scattered all over the country (four in the North, four in the Center, four in the South, and four in the Islands) was performed. Results The mean age of the patients was 58.3 years, with a sex ratio (male/female) of 1.5. HCV infection (also with other etiologies) continues to be the most prevalent etiology (58.1%). However, this prevalence was lower (P<0.01) than the corresponding figure (76.5%) for 2001. The proportion of hepatitis B virus-related cases almost doubled over time from 12.2% in 2001 to 22.5% in 2014 (P<0.01), most probably biased because of the distribution of entecavir and tenofovir free of charge at outpatient hospital clinics after 2001. Patients reporting risky alcohol intake (also with other etiologies) accounted for 12.4% of cases, a figure lower than that reported in 2001: 19.2% (P<0.01). The proportion of nonalcoholic fatty liver disease cases nearly doubled over time (3.6% in 2001 and 6.2% in 2014; P<0.05), reflecting the greater attention over time devoted to this syndrome. Conclusion The decreasing role of HCV infection as an etiologic factor of CH in Italy is good news considering the high cost of the directly acting antiviral agents for HCV eradication. Metabolic factors warrant greater attention in the near future.
The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14-16.7 kPa and were 4.49 kPa and 2.92-7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87-0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.