Regenerative Nodules Research Articles

Adipose-derived mesenchymal stem cells promote salivary duct regeneration via a paracrine effect

ObjectivesThe self-regeneration of exocrine tissues, including salivary glands, is limited and their regeneration mechanism has not yet been fully elucidated. Here we identify the role of adipose-derived mesenchymal stem cells (AMSCs) in salivary gland regeneration. MethodsAMSCs expressing mesenchymal stem cell markers were applied to a submandibular gland injury model and the mechanism of salivary gland repair and regeneration was analyzed. ResultsTransplanted green fluorescent protein (GFP)-labeled AMSCs grew tightly together and promoted ductal regeneration in the regenerative nodule, with slight infiltration of nonspecific immune cells. A comprehensive gene analysis through RNA-sequencing revealed increased expression of bone morphogenetic protein (BMP), transforming growth factor (TGF), and Wnt in AMSC-transplanted regenerative nodules. The factors released from AMSCs scavenge hydrogen peroxidase-induced reactive oxygen species (ROS) through Wnt promoter activity in vitro. Furthermore, AMSC-conditioned medium recovered the growth of the hydrogen peroxidase-damaged primordium of the submandibular gland culture ex vivo. ConclusionsThese results suggest that AMSC-released factors scavenge ROS and maintain salivary gland repair and regeneration via paracrine effects. Thus, AMSCs could be a practical and applicable tool for use in salivary gland regeneration.

Focal Liver Lesions other than Hepatocellular Carcinoma in Cirrhosis: Diagnostic Challenges.

Liver cirrhosis is associated with regenerative nodules and an increased risk of developing hepatocellular carcinoma (HCC). However, other benign and malignant liver lesions may also occur. Differentiating the other lesions from HCC is important for further therapeutic decisions. This review discusses the characteristics of non-HCC liver lesions in cirrhosis and their consequent appearance on contrast-enhanced ultrasonography (CEUS) with consideration of other imaging. Knowledge of this data would be helpful in avoiding misdiagnoses.

Cirrhosis and its Complication: other Clinical Complications Except ACLF and Critical Illness

Cirrhosis results from chronic liver disease, and is characterized by advanced fibrosis, scarring, and formation of regenerative nodules leading to architectural distortion. The main objective of the study is to find the cirrhosis and its complication, other clinical complications except ACLF and critical illness. This descriptive study was conducted at DHQ hospital, Vehari, Pakistan during June 2022 to January 2023. A comprehensive literature search of the published data was performed in regard with the spectrum, diagnosis, and management of cirrhosis and its complications. Data was also collected from OPD of the hospital record. We include all patients suffering from liver cirrhosis and its complication. It is concluded that patients with cirrhosis have progressive disease and suffer from multiple complications like ascites, HE, variceal bleeding, hepatorenal syndrome, cirrhotic cardiomyopathy, pulmonary syndromes, sarcopenia, frailty, and HCC. The prevention, early diagnosis, treatment, and palliation of these complications are essential in comprehensive clinical care plans.

Role of Tri-Phasic Computed Tomography in Evaluation of Hepatocellular Carcinoma Patients with Liver Cirrhosis

OBJECTIVESTo assess the usefulness of Tri-phasic computed tomography in the evaluation of hepatocellular carcinoma in cirrhotic patients.METHODOLOGYThis cross-sectional study was carried out in the Radiology and Imaging Department of Hayatabad Medical Complex Peshawar from October 2020 to September 2021 (01 year). Tri-phasic CT was done in all patients. Patients with suspected hepatocellular carcinoma diagnosed by clinical and ultrasonography and having high serum α-fetoprotein levels were enrolled in the study.RESULTSMalignant cases on tri-phasic CT were 120(82.8%) while benign cases were 25 (17.2%) Fig -I. In malignant tumor cases, 99(82.5%) patients had hepatocellular carcinoma (HCC), 13(10.8%) had metastases and 8(6.7%) had dysplastic nodule respectively. In benign tumour cases, 15(60%) had regenerative nodules, 6(24%) had hepatic adenoma and 4 (16%) had haemangioma. Tri -phasic CT as a tool in the diagnosis of hepatocellular carcinoma in cirrhotic patients showed a sensitivity of 96.8%, specificity of 79.7%, the accuracy of 95%, positive predictive values of 96.2% and negative predictive values of 88.1%.CONCLUSIONTri-Phasic CT can be an ideal diagnostic tool for detecting as well as characterizing hepatocellular carcinoma in cirrhotic patients.

S2753 Nodular Regenerative Hyperplasia-Induced Peristomal Variceal Bleeding: A Rare Thiopurine Side Effect

Introduction: Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are agents used to treat Inflammatory Bowel Disease (IBD). One of the rare side-effects described in cases throughout the literature is the development of Nodular Regenerative Hyperplasia (NRH) of the liver. NRH can lead to the development of non-cirrhotic portal hypertension (NCPH) which can then progress to ascites and varices. We present a patient who developed NRH from long-standing 6MP leading to peristomal variceal bleeding. Case Description/Methods: This case involves a 12 y/o male with fistulizing and stricturing Crohn’s disease, who was on 6-MP monotherapy from ages 14-18 and then restarted at age 27. At age 29, he underwent a partial colectomy with colostomy creation. Subsequently, he began to experience blood in his ostomy bag, which was later identified to be due to peristomal varices. Abdominal CT revealed lower esophageal varices and a nodular appearing liver. Liver biopsy then confirmed NRH, which had progressed to NCPH, and ultimately bleeding peristomal varices. The patient underwent a successful TIPS procedure with resolution of the varices and has not had any further bleeding. (Figure) Discussion: While there are a few cases of esophageal and gastric variceal bleeding due to NCPH secondary to thiopurine induced NRH, a case of peristomal variceal bleeding has yet to be described. NRH is a poorly understood condition that is characterized by diffuse transformation of normal liver parenchyma into small regenerative nodules with little to no fibrosis. Increased liver nodularity can cause NCPH and subsequently formation of varices throughout the GI tract. Patients with IBD on thiopurines have a cumulative incidence of NRH of 0.6% and 1.28% at 5 and 10 years, respectively1. NRH has a variable clinical presentation- from asymptomatic to severe complications of NCPH--and patients often do not present until late in the disease course. Several risk factors associated with development of NRH are male sex, stricturing and/or fistulizing disease, and history of a bowel resection. While NRH and its pursuing complications from thiopurines remains a rare entity, clinicians should be cognizant of this potential complication--particularly in those with fistulizing/stricturing disease and/or a surgical resection with an ostomy who present with gastrointestinal bleeding.Figure 1.: A – Digital subtraction angiographic (DSA) image shows catheter-directed venography of a dilated branch of the inferior mesenteric vein (IMV) that supplies a network of peristomal varices (black arrow). B - After successful creation of a transjugular intrahepatic portosystemic shunt (TIPS) with a covered stent (white arrow), a DSA image shows a plug and foam (black arrow) in the dilated IMV branch with decreased blood flow into the peristomal varices. C- Final DSA image of completion IMV venography shows absent blood flow into the dilated IMV branch and peristomal varices.

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

Evaluation of thyroid hormones in liver cirrhosis patients on the basis of child pugh score

Introduction: Cirrhosis is an advanced stage of liver fibrosis that is accompanied by distortion of the hepatic vasculature. It is the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. Objectives: The study was intended to assess serum Triiodothyronine (T3), Thyroxine (T4) levels and Thyroid Stimulating Hormone (TSH) on the basis of Child Pugh Score in patients with Liver Cirrhosis. Methodology: 100 clinically diagnosed cases of Liver Cirrhosis patients were enrolled for the study. Estimation of Thyroid Hormones were performed. Statistical evaluation was done for analysis of the results. Result: The study documented a significant decrease in T3 levels (P= <0.0001), a non-significant increase in T4 levels (P=0.997) and a slightly significant increase in TSH levels (P=0.034) on the basis of CP Score. Conclusion: The patients with liver cirrhosis have significantly decreased levels of T3 with increased CP Score. The routine liver enzymes like AST, ALT and ALP may be unable to predict the risk of development of liver cirrhosis specially in the early stages. Therefore, screening of serum T3 levels is strongly recommended in patients with early-stage liver diseases like ALD, NAFLD, NASH and CLD.

Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats

AimsLiver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. Materials and methodsBile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2–related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. Key findingsThe chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SignificanceAtorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.

HCC or Something Else? Frequency of Various Benign and Malignant Etiologies in Cirrhotic Patients with Newly Detected Focal Liver Lesions in Relation to Different Clinical and Sonographic Parameters.

Background and Aims: To investigate the frequency of different benign and malignant focal liver lesions (FLLs) in relation to clinical and sonographic features among patients with liver cirrhosis (LC) and newly detected FLLs. Methods: This study was a retrospective analysis of 225 cirrhotic patients with newly detected FLLs who underwent hepatic ultrasound (US) examinations at our university hospital from 2011 to 2022. The diagnosis of FLLs was based on histology and/or consensus radiological criteria, in accordance with the current diagnostic guidelines. The FLLs were classified into benign (bFLLs) or malignant (mFLLs) lesions and the latter group was subclassified into HCC and non-HCC mFLLs. The frequency, clinical parameters, and sonographic features of the different groups were examined and compared. Results: Of the 225 FLLs, 154 (68.4%) were mFLLs and 71 (31.6%) bFLLs. HCC was the most frequent subcategory of FLLs (132; 58.7%). There were (22; 9.8%) non-HCC mFLLs with 11 (4.9%) metastases and 11 (4.9%) non-HCC primary liver tumors. Regenerative nodules (RNs) were the most frequent form of bFLLs (25; 11.1%), followed by simple cysts (22; 9.8%) and hemangiomas (14; 6.2%). The other bFLLs (10; 14.1%) were fat deposition/sparing (5), hematomas (2), abscesses (2), and echinococcal cysts (1). The distribution of bFLLs and HCC and non-HCC mFLLs varied significantly according to the clinical scenarios. HCC mFLLs were more frequent in males (p = 0.001), in those with no history of active non-hepatic primary malignant disease (NHPMD) (p < 0.001), in those with a hepatitis B or C etiology of LC (p = 0.002), when located in the right lobe (p = 0.008), and when portal vein thrombosis was present (p = 0.03). Conclusion: In cirrhotic patients with newly detected FLLs, the non-HCC etiology was more frequently diagnosed in lesions that were located in the left lobe, in females, and in patients with a history of active NHPMD. Thus, the lower frequency of HCC in the abovementioned groups demonstrated that a cautious implementation of the current consensus radiological criteria would be required for these groups, particularly in patients with an active NHPMD, given the fact that the consensus criteria were not validated in these populations. A more active diagnostic approach may ultimately be needed for these patients. Large prospective studies are needed to validate these findings.

Non endoscopic predictor of esophageal varices in patients with cirrhosis of liver from tertiary care hospital

With the rising mortality rate, worldwide liver cirrhosis has been ranked as the 13th leading cause of mortality. Portal hypertension is one of the common consequences of liver cirrhosis. Further, portal hypertension has its own complications and the most serious among them is the risk of development of esophageal varices (EV) caused by increased hepatic vascular resistance related to hepatic fibrosis and regenerative nodules. To identify the non-endoscopic predictor of esophageal varices in patients with liver cirrhosis in a tertiary care hospitalA prospective study was carried out at the tertiary care hospital of Dr. PDMMC, Amravati between the period September 2018 to March 2020. One hundred patients diagnosed with liver cirrhosis were taken for the study. The patients were selected based on the clinical, the radiological and historical data. The patients were divided into two groups, namely the small size of varices group where n=71 and large size of varices group where n=29. Factors such as platelet count, serum albumin, spleen (cm), PV (mm), platelet count and child-pugh classification were considered important as their p values were less than 0.05.The platelet count and the spleen size showed the difference among the patients belonging to small varices and larger varices group, respectively. Ascites was noted in 90% of the cases. 65% of the patients suffered from portal gastropathy and esophageal varices.

The role of glypican 3, arginase 1, and CD34 in differentiation between benign and malignant primary hepatic lesions

Background and aim Benign hepatic nodular lesions mimicking hepatocellular carcinoma (HCC) may be categorized into hyperplastic nodular lesions, neoplastic nodular lesions, and miscellaneous nodular lesions. This study aimed to assess the role of glypican 3 (GPC3), arginase 1 (ARG-1), and CD34 in differentiation between benign and malignant primary hepatic lesions. Materials and methods This study included 48 cases, where 25 (52.08%) cases were diagnosed as primary HCC in the liver and 23 (47.92%) cases were diagnosed as benign hepatic lesions. Of the 48 patients, five (10.42%) cases were diagnosed as focal nodular hyperplasia, four (8.33%) cases were diagnosed as hepatic adenoma, eight (16.67%) cases were diagnosed as dysplastic nodule, and six (12.50%) cases were diagnosed as regenerative nodule. Results The sensitivity of GPC3 for differentiation between benign and malignant primary hepatic lesions was 80% and its specificity was 82.5%. The sensitivity of ARG-1 was 90%, and its specificity was 0.0%. The sensitivity of CD34 for HCC in the study group was 84% and its specificity was 91.3%. Conclusion There was high sensitivity and specificity of both GPC3 and CD34 immunostaining for distinction of primary HCC from benign hepatic mimicker lesions, whereas there was high sensitivity of ARG-1 in both benign and malignant primary hepatic lesions but with no specificity for differentiating the benign from malignant primary hepatic lesions.

State-of-the-art review on the correlations between pathological and magnetic resonance features of cirrhotic nodules.

Hepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features.

Analysis of Quantitative Data of Arterial Spin Labeling Perfusion of the Liver at Admission and Follow up of Patients with Viral Cirrhosis

The aim of this work is to analyze quantitative data of magnetic resonance ASL-perfusion of the liver at admission and follow up of patients with viral cirrhosis.The study included 34 patients with viral liver cirrhosis: 23 (67.6 %) men and 11 (32.4 %) women. All subjects underwent abdominal ultrasound with Dopplerography of the abdominal vessels, shear wave elastography, Arterial spin Labeling (ASL) — Perfusion of the liver by magnetic resonance imaging. Post-processing of ASL-perfusion images was carried out, their quantitative assessment in regenerative liver nodules and the parenchyma structure was carried out. It was found that for patients with liver cirrhosis according to Child-Pugh Class A, regardless of the degree of activity, the values of ASL-perfusion of the liver were 99.6 ± 1.8 ml/100g/min, with class B — 95.6 ± 4.9 ml/100g/min, with class C — 98.5 ± 2.6 ml/100g/min. To determine the diagnostic significance of liver ASL-perfusion, a generalized prognosis ratio ΔM = MNBF/ MHBF was calculated, where MNBF is a quantitative indicator of volumetric blood flow in the regenerative nodule, MHBF is a quantitative indicator of volumetric hepatic blood flow in the surrounding parenchyma. The results obtained by ASL-perfusion were compared with the data of shear wave elastography.For patients with viral liver cirrhosis the quantitative indicator of ASL-perfusion of the liver is less than 101.4 ml/100g/min. To predict the course of viral etiology cirrhosis, the prognosis ratio ΔM should be taken, and if ΔM &gt; 1, this indicates a poor prognosis (fibrosis progression), if ΔM ≤ 1 — a favorable one (no fibrosis progression). Diagnostic and prognostic significance of ASL-liver perfusion for patients with viral cirrhosis at admission to the hospital — AUROC = 0.865 (95 % CI 0.843–0.928) and follow up — AUROC = 0.915 (95 % CI 0.881–0.946).

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Clinical Profile of Cirrhosis of Liver with Special Reference to Bacteriological Profile of Patients at a Government Tertiary Care Center in Maharashtra

Background: Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury that leads to portal hypertension and end stage liver disease. The exact prevalence of cirrhosis worldwide is unknown. Cirrhosis prevalence was estimated at 0.15% or 400,000 in the USA where it accounted for more than 25,000 deaths and 373,000 hospital discharges in 1998. This may be an underestimation as we recognize the high prevalence of undiagnosed cirrhosis in both NASH and hepatitis C. Similar numbers have been reported from Europe, and numbers are even higher in most Asian and African countries where chronic viral hepatitis B or C are frequent. Since compensated cirrhosis often goes undetected for prolonged periods of time, a reasonable estimate is that up to 1% of populations may have histological cirrhosis. Aim: To study clinical profile of cirrhotic patients. Material and Methods: A cross-sectional observational study was carried out at Inpatient Department of Medicine of tertiary care hospital. Total 100 cases were studied. Registration of patients was from October, 2019 to March 2021. They were registered when admitted under Medicine department. At the time of registration, the patients with exclusion criteria were not enrolled for study. The main objective of this study is to study the biochemical and bacteriological profile of cirrhotic patients. At the time of registration, the baseline information was taken especially with respect to sociodemographic factors, clinical findings, and other investigations. The data thus collected was analysed to study clinical profile of cirrhotic patients. Results: Mean age in years was 55.1 +15.06, ranging from 24 to 75. Majority 40% were in age group of 40 to 60 years. Majority 68% were males and 32% were females. Mean SBP was 150.15+21.54 ranging from 100 to 210. 66% had increased SBP i.e.&gt;140 mm of Hg and Mean DBP was 91.64+11.87, ranging from 60 to112. ...........

Risk factors for developing hepatocellular carcinoma in patients treated with direct-acting antivirals

Introduction and aimChronic hepatitis C is one of the main causes of cirrhosis of the liver. Treatment with direct-acting antivirals (DAAs) improves survival. There is controversy as to whether AADs create an increased risk for the development of hepatocellular carcinoma (HCC). The aim of the present study was to determine the risk factors for developing HCC in patients with chronic hepatitis C treated with DAAs. Materials and methodsA cohort study was conducted, within the time frame of June 2017 and June 2018, on patients >18 years of age, with chronic hepatitis C, genotypes 1 and 4, with one year of follow-up, to evaluate the presence of HCC. ResultsWe analyzed 108 patients, 71 (65%) of whom were women. Mean patient age was 56.24 years (±10.6), 1b was the most frequent genotype (63%), and 49% of the patients received treatment with DAAs (ombitasvir/paritaprevir/ritonavir plus dasabuvir). Thirty-four (31%) patients were obese. Fifty-three percent (58) had cirrhosis and 82% (89) had Child-Pugh class A liver function. Sustained virologic response at 12 weeks was 100%. Eight (7%) patients developed HCC and 1b was the most frequently associated genotype (87%). The presence of regenerative nodules >10 mm (P < .05), esophageal varices (P < .05), cirrhosis of the liver (P < .05), Child-Pugh B-C (P < .05), and alpha-fetoprotein >20 IU/mL (P = 0.20) one year after treatment were associated with the development of HCC. ConclusionsThe risk factors for developing HCC were the presence of cirrhosis of the liver, Child-Pugh class B liver function, esophageal and/or gastric varices, and genotype 1b.

Hepatocellular Carcinoma in Evolution: Correlation with CEUS LI-RADS

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a high incidence worldwide and a high associated mortality. Well-recognized risk factors that cause a predisposition to the development of HCC include chronic infection with the hepatitis B or C virus, alcohol-related and non-alcohol-related fatty liver disease, and cirrhosis. In these chronically diseased livers, benign regenerative nodules can increase in size and develop cellular atypia that progress into dysplastic nodules and ultimately HCC. This sequence of hepatocarcinogenesis is coupled with changes in nodule vascularity, including progressive decreased density of portal triads and induced neoangiogenesis, resulting in increased hepatic arterial recruitment. Changes in vascularity result in an array of patterns of nodule enhancement and washout, which can be sensitively depicted with dynamic real-time contrast-enhanced US. Regenerative nodules are isoenhancing relative to the liver with all phases, while HCC classically shows avid arterial phase hyperenhancement with late mild washout. In between, there is great variation as nodules evolve through progressive grades of dysplasia toward HCC. Observed patterns of enhancement and washout can be used to diagnose or stratify the risk of malignancy in liver nodules by using the diagnostic algorithm described by the American College of Radiology Liver Imaging Reporting and Data System (LI-RADS). This facilitates the detection and close monitoring of potential early-stage disease. LI-RADS categorizes nodules according to a probabilistic likelihood for HCC with criteria for LR-5 nodules that are highly specific for the diagnosis of HCC, allowing treatment without exposing the patient to invasive biopsy. An invited commentary by Fetzer is available online. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Focal liver lesions in cirrhosis: Role of contrast-enhanced ultrasonography.

Contrast-enhanced ultrasound (CEUS) represents a great innovation for the evaluation of focal liver lesions (FLLs). The main advantage of CEUS is the real-time imaging examination and the very low toxicity in patients with renal failure. Liver cirrhosis has been recognized as a major risk factor for the onset of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). HCC in liver cirrhosis develops as the last step of a complex that leads to the gradual transformation from regenerative nodule through dysplastic nodule to HCC. In patients with liver cirrhosis, a surveillance program is recommended consisting of ultrasound (US) for detecting small focal lesions. A wide spectrum of benign and malignant lesions other than HCC may be found in the cirrhotic liver and their differentiation is important to avoid errors in staging diseases that may preclude potentially curative therapies. Several published studies have explored the value of CEUS in liver cirrhosis and they have been shown to have excellent diagnostic and prognostic performances for the evaluation of non-invasive and efficient diagnosis of FLLs in patients at high risk for liver malignancies. The purpose of this article is to describe and discuss CEUS imaging findings of FLLs including HCC and ICC, all of which occur in cirrhotic livers with varying prevalence.

Factores de riesgo para desarrollar carcinoma hepatocelular en pacientes tratados con antivirales de acción directa

Introduction and aimChronic hepatitis C is one of the main causes of cirrhosis of the liver. Treatment with direct-acting antivirals (DAAs) improves survival. There is controversy as to whether AADs create an increased risk for the development of hepatocellular carcinoma (HCC). The aim of the present study was to determine the risk factors for developing HCC in patients with chronic hepatitis C treated with DAAs. Materials and methodsA cohort study was conducted, within the time frame of June 2017 and June 2018, on patients >18 years of age, with chronic hepatitis C, genotypes 1 and 4, with one year of follow-up, to evaluate the presence of HCC. ResultsWe analyzed 108 patients, 71 (65%) of whom were women. Mean patient age was 56.24 years (±10.6), 1b was the most frequent genotype (63%), and 49% of the patients received treatment with DAAs (ombitasvir/paritaprevir/ritonavir plus dasabuvir). Thirty-four (31%) patients were obese. Fifty-three percent (58) had cirrhosis and 82% (89) had Child-Pugh class A liver function. Sustained virologic response at 12 weeks was 100%. Eight (7%) patients developed HCC and 1b was the most frequently associated genotype (87%). The presence of regenerative nodules >10mm (P<.05), esophageal varices (P<.05), cirrhosis of the liver (P<.05), Child-Pugh B-C (P<.05), and alpha-fetoprotein >20IU/ml (P=0.20) one year after treatment were associated with the development of HCC. ConclusionsThe risk factors for developing HCC were the presence of cirrhosis of the liver, Child-Pugh class B liver function, esophageal and/or gastric varices, and genotype 1b.

Perfusion-Diffusion Ratio: A New IVIM Approach in Differentiating Solid Benign and Malignant Primary Lesions of the Liver.

Introduction In order to improve the efficacy of intravoxel incoherent motion (IVIM) parameters in characterising specific tissues, a new concept is introduced: the perfusion–diffusion ratio (PDR), which expresses the relationship between the signal S(b) decline rate as a result of IVIM and the rate of signal S(b) decline due to diffusion. The aim of this study was to investigate this novel approach in the differentiation of solid primary liver lesions. Material and Methods. Eighty-three patients referred for liver MRI between August 2017 and January 2020 with a suspected liver tumour were prospectively examined with the standard liver MRI protocol extended by DWI-IVIM sequence. Patients with no liver lesions, haemangiomas, or metastases were excluded. The final study population consisted of 34 patients with primary solid liver masses, 9 with FNH, 4 with regenerative nodules, 10 with HCC, and 11 with CCC. The PDR coefficient was introduced, defined as the ratio of the rate of signal S(b) decrease due to the IVIM effect to the rate of signal S(b) decrease due to the diffusion process, for b = 0. Results No significant differences were found between benign and malignant lesions in the case of IVIM parameters (f, D, or D∗) and ADC. Significant differences were observed only for PDR, with lower values for malignant lesions (p = 0.03). The ROC analysis yielded an AUC value for PDR equal to 0.74, with a cut-off value of 5.06, sensitivity of 81%, specificity of 77%, and accuracy of 79%. Conclusion PDR proved to be more effective than IVIM parameters and ADC in the differentiation of solid benign and malignant primary liver lesions.