Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review.

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous-portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.

Child-Pugh Class and Not Thrombocytopenia Impacts the Risk of Complications of Endoscopic Band Ligation in Patients with Cirrhosis and High Risk Varices.

Background and Aims: Endoscopic band legation (EBL) is an effective method for the prophylaxis of acute variceal bleeding (AVB). This procedure may be associated with several complications, particularly bleeding. Our analysis aimed to evaluate the risk of complications due to EBL in a cohort of patients who underwent EBL for the prophylaxis of variceal bleeding and the eventual presence of risk predictors. Patients and Methods: We retrospectively analysed data from consecutive patients who underwent EBL in a primary prophylaxis regimen. For all patients, simultaneously with EBL, we recorded the Child-Pugh and MELD score, platelet count and US features of portal hypertension. Results: We collected data from 431 patients who performed a total of 1028 EBLs. We recorded 86 events (8.4% of all procedures). Bleeding after EBL occurred 64 times (6.2% of all procedures), with the following distribution: intraprocedural bleeding in 4%; hematocystis formation in 17 cases (1.7%); 6 events (0.6%) of AVB due to post-EBL ulcers. None of these events presented a correlation with platelet count (84,235 ± 54,175 × 103/mL vs. 77,804 ± 75,949 × 103/mL; p = 0.70) or with the condition of severe thrombocitopenia established at PLT < 50,000/mmc (22.7% with PLT ≤ 50,000/mmc vs. 15.9% with PLT ≥ 50,000/mmc; p = 0.39). Our results showed a relationship between cumulative complications of EBL and Child-Pugh score (6.9 ± 1.6 vs. 6.5 ± 1.3; p = 0.043). Conclusions: EBL in cirrhotic patients is a safe procedure. The risk of adverse events depends on the severity of liver disease, without a relationship with platelet count.

Heart rate variability is associated with disease severity and portal hypertension in cirrhosis.

INTRODUCTION: Autonomic nervous system activity in cirrhotic portal hypertension is linked to hyperdynamic circulation. Heart rate variability (HRV) is a validated noninvasive method to assess the sympathovagal balance. To investigate the correlation between HRV parameters and degree of portal hypertension, we studied a cohort of patients with cirrhosis accounting for etiology and treatments. PATIENTS AND METHODS: In this cross-sectional, observational cohort study, 157 outpatients of both sex with nonalcoholic cirrhosis were assessed by upper gastrointestinal endoscopy to search for esophagogastric varices. Twenty-four-hour electrocardiogram Holter monitoring with 3 HRV parameters measurement [SD of the NN intervals, root mean square successive difference of NN intervals, and SD of the averages of NN intervals (SDANN)] according to time-domain analysis were performed in all patients. Sixteen patients with large esophagogastric varices underwent measurements of the HVPG and assessment of HRV parameters at baseline and after 45 days on carvedilol. RESULTS: The liver dysfunction, expressed by Child-Pugh class or MELD score, was directly related to root mean square successive difference of NN intervals and inversely related to SDANN. Presence of ascites was inversely related to SDANN and to SD of the NN intervals. Treatment with carvedilol had an inverse relation with SDANN. Presence and size of esophagogastric varices had an inverse relation to SDANN and SD of the NN intervals. Upon multivariate analysis the associations between SDANN and Child-Pugh class, size of varices and ascites were confirmed. In the subgroup of 16 patients undergoing HVPG measurement, pressure gradient was unrelated to heart rate and HRV parameters. CONCLUSIONS: Time-domain HRV parameters in patients with cirrhosis, confirm the autonomic nervous system alteration, and their correlation to the degree of portal hypertension suggesting a role of the ANS in hepatic decompensation.

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

INTRODUCTION: Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria). METHODS: All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 10 9 /L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 10 9 /L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated. RESULTS: The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria. DISCUSSION: Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

Effects of Eradicating Hepatitis C Virus Infection in Patients With Cirrhosis Differ With Stage of Portal Hypertension.

BACKGROUND & AIMS: Clearance of hepatitis C virus (HCV) via antiviral treatment changes the course of liver disease. We evaluated the benefit of sustained virologic response (SVR) in patients with HCV and cirrhosis without (stage 1) and with (stage 2) esophageal varices (EV). METHODS: We performed a prospective cohort study of 444 patients with HCV and compensated cirrhosis (218 with stage 1 and 226 with stage 2 disease) treated with peg-interferon and ribavirin from June 2001 through December 2009 at the University of Palermo, Italy and followed for a median of 7.6 years (range, 1-12.6 years). We used Cox regression analysis to identify variables associated with appearance or progression of EVs, development of hepatocellular carcinoma (HCC), liver decompensation, and overall survival. RESULTS: In the intention-to-treat analysis, 67 patients with stage 1 disease (30.7%) and 41 patients with stage 2 disease (18.1%) achieved an SVR (P = .003). Patients with stage 1 disease and an SVR were less likely to develop EVs than stage 1 patients without an SVR (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11-0.48; P < .001). However, SVR did not affect whether patients with stage 2 disease developed further EVs (HR, 1.58; 95% CI, 0.33-1.03; P = .07, by log-rank test). An SVR was associated with lower risk for HCC (HR, 0.25; 95% CI, 0.12-0.55; P < .001). Patients with stage 2 disease, regardless of SVR, were at greater risk than patients with stage 1 disease for liver decompensation (HR, 2.82; 95% CI, 1.73-4.59; P < .001) or death (HR, 1.77; 95% CI, 1.12-2.80; P = .015). A lower proportion of patients with stage 1 disease and an SVR died from HCC (2.9%), compared with those without an SVR (11.9%) (P = .03) or developed liver decompensation (none vs 7.1% without an SVR; P = .009). A lower proportion of patients with stage 2 disease and an SVR died from causes secondary to HCC (2.0%) compared with those without an SVR (18.4%) (P = .003). Death from causes secondary to liver decompensation did not differ significantly between patients with stage 2 disease with or without an SVR (12.1% vs 25.4%; P = .15). CONCLUSIONS: In a prospective study of 444 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, HCC, and death, regardless of whether the patients had EVs.

Oesophagogastroduodenoscopy in patients with cirrhosis: Extending the range of detection beyond portal hypertension.

BACKGROUND: Oesophagogastroduodenoscopy is currently recommended for the screening of varices in cirrhosis. In addition to the assessment of varices, oesophagogastroduodenoscopy can detect conditions that, while unrelated to portal hypertension, may require treatment. AIMS: We evaluated in a large cohort of cirrhotic patients the prevalence of upper digestive findings other than oesophagogastric varices, the associations between upper gastrointestinal findings, portal hypertension and features of cirrhosis, and the incidence of new lesions in the course of a surveillance program. METHODS: Analysis of the records of 611 consecutive cirrhotic patients undergoing oesophagogastroduodenoscopy for screening and surveillance. RESULTS: 232 patients (38%) presented endoscopic lesions not related to portal hypertension: peptic diseases (n=193), proliferative diseases (n=27) and vascular diseases (n=12). In the screening group, 127 patients (39.4%) had pathologic lesions. At multivariate analysis, an association was found between peptic diseases and the absence of portal hypertensive gastropathy (RR 3.3; 95% CI 2.2-4.8); vascular diseases were associated with endoscopic signs of portal hypertension (p=0.01). During surveillance, 9/55 patients (16.3%) in the group without previous pathologic findings developed new lesions. CONCLUSIONS: Oesophagogastroduodenoscopy in patients with cirrhosis undergoing endoscopy for screening diagnosed pathologic lesions unrelated to portal hypertension requiring a change in management in 39.4% of asymptomatic subjects.

Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis.

UNLABELLED: Indirect methods to predict the presence of esophageal varices (EV) in patients with cirrhosis are not sensitive enough to be used as a surrogate for endoscopy. We tested the effectiveness of liver stiffness measurement (LSM) by transient elastography and the presence of insulin resistance (IR), a marker associated with fibrosis progression, in the noninvasive prediction of portal hypertension. One hundred four consecutive patients with newly diagnosed Child A hepatitis C virus (HCV) cirrhosis underwent upper gastrointestinal endoscopy to search for EV. Clinical, anthropometric, biochemical, ultrasonographic, and metabolic features, including IR by the homeostasis model assessment (HOMA), and LSM by transient elastography, were recorded at the time of endoscopy. EVs were detected in 63 of 104 patients (60%). In 10 patients (16%), the EVs were medium-large (>or=F2). By multivariate analysis, the presence of EVs was independently associated with a low platelet count/spleen diameter ratio (OR, 0.998; 95% CI, 0.996-0.999) and a high HOMA-IR score (OR, 1.296; 95%CI, 1.018-1.649), not with LSM (OR, 1.009; 95%CI, 0.951-1.070). It is noteworthy that nine of ten patients with medium-large EVs had a platelet/spleen ratio of less than 792 or an HOMA-IR of greater than 3.5. The independent association between low platelet count/spleen diameter ratio (OR, 0.998; 95%CI, 0.996-1.000), high HOMA-IR score (OR, 1.373; 95%CI, 1.014-1.859) and presence of EV was confirmed in the subgroup of 77 nondiabetic subjects. CONCLUSIONS: In patients with Child A HCV cirrhosis, two simple, easy-to-get tests, namely the platelet/spleen ratio and insulin resistance measured by HOMA-IR, regardless of the presence of diabetes, significantly predict the presence of EV, outweighing the contribution given by transient elastography.