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Background Liver cirrhosis is the fourth cause of death in adults in Western countries, with complications of portal hypertension being responsible for most casualties. In order to reduce mortality, development of accurate diagnostic methods for early diagnosis, effective etiologic treatment, improved pharmacological therapy for portal hypertension, and effective therapies for end-stage liver failure are required. Discussion Early detection of cirrhosis and portal hypertension is now possible using simple non-invasive methods, leading to the advancement of individualized risk stratification in clinical practice. Despite previous assumptions, cirrhosis can regress if its etiologic cause is effectively removed. Nevertheless, while this is now possible for cirrhosis caused by chronic hepatitis C, the incidence of cirrhosis due to non-alcoholic steatohepatitis has increased dramatically and effective therapies are not yet available. New drugs acting on the dynamic component of hepatic vascular resistance are being studied and will likely improve the future management of portal hypertension. Conclusion Cirrhosis is now seen as a dynamic disease able to progress and regress between the compensated and decompensated stages. This opinion article aims to provide the author’s personal view of the current major advances and challenges in this field.

Given the well-known limitations of liver stiffness measurement (LSM),[ 1] spleen stiffness measurement (SSM) using the standard liver 50-Hz module on vibration controlled transient elastography (FibroScan; Echosens) was first proposed by Stefanescu et al. in 2011[ 2] as a potential additional noninvasive tool (NIT) to assess the presence/absence of high-risk varices. Since the first publication, several other authors have tested SSM, showing that it correlates hepatic venous pressure gradient (HVPG) with the size of esophageal varices and with liver-related events in patients with compensated advanced chronic liver disease (cACLD). [...]importantly, SSM using the standard 50-Hz liver module fails in 10%–27% of cases and is almost invariably not applicable to normal size spleens. [...]in this population, a SSM@100 Hz for the XL probe would be a useful development.

The concept of ‘cirrhosis’ is evolving and it is now clear that compensated and decompensated cirrhosis are completely different in terms of prognosis. Furthermore, the term ‘advanced chronic liver disease (ACLD)’ better reflects the continuum of histological changes occurring in the liver, which continue to progress even after cirrhosis has developed, and might regress after removing the etiological factor causing the liver disease. In compensated ACLD, portal hypertension marks the progression to a stage with higher risk of clinical complication and requires an appropriate evaluation and treatment. Invasive tests to diagnose cirrhosis (liver biopsy) and portal hypertension (hepatic venous pressure gradient measurement and endoscopy) remain of crucial importance in several difficult clinical scenarios, but their need can be reduced by using different non-invasive tests in standard cases. Among non-invasive tests, the accepted use, major limitations and major benefits of serum markers of fibrosis, elastography and imaging methods are summarized in the present review.

Chronic liver diseases pose a serious public health issue. Identifying patients at risk for advanced liver fibrosis is crucial for early intervention. The Fibrosis-4 score (FIB-4), a simple non-invasive test, classifies patients into three risk groups for advanced fibrosis. This study aimed to estimate the prevalence of patients at risk for advanced hepatic fibrosis at a Swiss tertiary care hospital by calculating the FIB-4 score in routine blood analysis. A retrospective study was conducted using data from 36,360 patients who visited outpatient clinics at eight main clinics of the University Hospital Bern in Switzerland. The data collection period ran from January 1st to December 31st, 2022. Patients attending the hepatology outpatient clinic were excluded. We then calculated the overall and clinic-specific prevalence of patients falling into the high risk category for advanced fibrosis according to FIB-4. Among the 36,360 patients, 26,245 (72.2%) had a low risk of advanced fibrosis (FIB-4 <1.3), whereas 3913 (10.8%) and 2597 (7.1%) patients were flagged to have a high risk of advanced fibrosis (FIB-4 >2.67 and FIB-4 >3.25 respectively). Geriatrics and Cardiology had the highest proportions of patients at risk for advanced fibrosis over all clinics. This study demonstrates a high prevalence of high FIB-4 score in a Swiss tertiary care hospital. The implementation of the automatically generated FIB-4 score in daily practice, not only in primary care, but also within tertiary care hospitals, could be crucial for early identification of outpatients at high risk of advanced liver fibrosis requiring further hepatological investigations.

Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child–Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126–0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.

Hepatic venous pressure gradient (HVPG) is the most useful parameter for the assessment of patients with cirrhosis. HVPG provides diagnostic and prognostic information in several clinical scenarios: treatment of portal hypertension, surgery for hepatocellular carcinoma, treatment of HCV-related or HBV-related cirrhosis, and outcome of recurrent HCV infection after liver transplantation. Portal hypertension is a severe, almost unavoidable complication of chronic liver diseases and is responsible for the main clinical consequences of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to ≥10 mmHg; above this threshold, the complications of portal hypertension might begin to appear. Measurement of HVPG is increasingly used in clinical hepatology, and numerous studies have demonstrated that the parameter is a robust surrogate marker for hard clinical end points. The main clinical applications for HVPG include diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who experience a reduction in HVPG of ≥20% or to <12 mmHg in response to drug therapy are defined as 'responders'. Responders have a markedly decreased risk of bleeding (or rebleeding), ascites, and spontaneous bacterial peritonitis, which results in improved survival. Key Points Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard technique for evaluation of portal hypertension in liver disease In patients with cirrhosis, HVPG measurement provides independent prognostic information on survival and the risk of decompensation The HVPG response to pharmacological therapy enables the identification of patients with portal hypertension who are most likely to benefit from treatment Measurement of HVPG helps to assess the risk of liver failure and death after liver resection in patients with compensated chronic liver disease or hepatocarcinoma No noninvasive alternatives to HVPG measurement are currently available

PurposePatients with morbid obesity are at high risk of liver fibrosis due to metabolic-associated fatty liver disease. Data on liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by vibration-controlled transient elastography (VCTE, FibroScan®) XL probe for liver fibrosis and steatosis assessment in morbid obesity are needed.Materials and MethodsLSM and CAP were measured in candidates to bariatric surgery at a single center during 12 months. In patients who underwent an intraoperative liver biopsy, we compared LSM and CAP with histology findings. Comorbidities, body mass index, type of surgery, and infections after surgery were collected and analyzed.ResultsOf the eighty-three patients assessed by XL probe, 49 (59%; female in 63%, BMI 42.6 ± 5.1 kg/m2) had a valid LSM and CAP measurement. LSM was 7.0 ± 3.9 kPa and CAP 329 ± 57 dB/m. In the 14 patients undergoing intraoperative liver biopsy, all had steatosis (severe in 50%), 6 (43%) had NASH (NAS ≥ 5), and 4 (29%) showed significant or bridging fibrosis. LSM accurately discriminated between patients with and without significant or severe fibrosis (AUROC 0.833) and CAP well-identified patients with or without ≥S2 steatosis (AUROC 0.896). Nine of 49 patients (18%) tested positive for significant/severe fibrosis by LSM (cut-off 8.9 kPa).ConclusionApplicability of LSM and CAP by XL probe in patients candidate to bariatric surgery was moderate. However, when technically successful, their reliability to diagnose severe steatosis and fibrosis related to MAFLD was good.

Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.

We evaluated the effectiveness of automated segmentation of the liver and its vessels with a convolutional neural network on non-contrast T1 vibe Dixon acquisitions. A dataset of non-contrast T1 vibe Dixon liver magnetic resonance images was labelled slice-by-slice for the outer liver border, portal, and hepatic veins by an expert. A 3D U-Net convolutional neural network was trained with different combinations of Dixon in-phase, opposed-phase, water, and fat reconstructions. The neural network trained with the single-modal in-phase reconstructions achieved a high performance for liver parenchyma (Dice 0.936 ± 0.02), portal veins (0.634 ± 0.09), and hepatic veins (0.532 ± 0.12) segmentation. No benefit of using multi-modal input was observed (p = 1.0 for all experiments), combining in-phase, opposed-phase, fat, and water reconstruction. Accuracy for differentiation between portal and hepatic veins was 99% for portal veins and 97% for hepatic veins in the central region and slightly lower in the peripheral region (91% for portal veins, 80% for hepatic veins). In conclusion, deep learning-based automated segmentation of the liver and its vessels on non-contrast T1 vibe Dixon was highly effective. The single-modal in-phase input achieved the best performance in segmentation and differentiation between portal and hepatic veins.

Purpose To analyze whether the T1 relaxation time of the liver is a good predictor of significant liver fibrosis and whether normalization to the blood pool improves the predictive value. Methods This prospective study was conducted between 03/2016 and 02/2018. One hundred seventy-three patients underwent multiparametric liver MRI at 3 T. The T1 relaxation time was measured in the liver and the spleen, in the aorta, the portal vein, and the inferior vena cava (IVC). T1 relaxation times with and without normalization to the blood pool were compared between patients with ( n  = 26) and without ( n  = 141) significant liver fibrosis, based on a cutoff value of 3.5 kPa in MRE as the noninvasive reference standard. For statistics, Student’s t test, receiver operating characteristic (ROC) curve analysis, and Pearson’s correlation were used. Results The T1 relaxation time of the liver was significantly longer in patients with liver fibrosis, both with and without blood pool normalization ( p  < 0.001). T1 relaxation time of the liver allowed prediction of significant liver fibrosis (AUC = 0.88), while normalization to the IVC resulted in a slightly lower performance (AUC = 0.82). The lowest performance was achieved when the T1 relaxation times of the liver were normalized to the aorta (AUC = 0.66) and to the portal vein (AUC = 0.62). The T1 relaxation time of the spleen detected significant liver fibrosis with an AUC of 0.68, and 0.51–0.64 with normalization to the blood pool. Conclusion The T1 relaxation time of the liver is a good predictor of significant liver fibrosis. However, normalization of the blood pool did not improve the predictive value. Key Points • The T1 relaxation time of the liver is a good predictor of significant liver fibrosis. • Normalization to the blood pool did not improve the predictive value of T1 mapping. • If the blood pool normalization was weighted 30% to the aorta and 70% to the portal vein, the performance was better than normalization to the aorta alone but still lower than normalization to the IVC.