Development Of Hepatic Decompensation Research Articles

No value of non-selective beta-blockers after TIPS-insertion.

Non-selective beta-blockers (NSBB) are a well-established treatment in patients with clinically significant portal hypertension. However, their potential role after insertion of a transjugular intrahepatic portosystemic shunt (TIPS) still needs to be determined. Of note, recent studies suggested that favourable anti-inflammatory effects of NSBB might be independent from pressure reduction. This study aimed to evaluate whether NSBB-treatment is associated with amelioration of systemic inflammation (SI), hepatic decompensation and survival after TIPS-insertion. In a retrospective study comprising 305 consecutive patients, we investigated the impact of NSBB-intake at TIPS-placement on periinterventional cirrhosis-associated complications and continued NSBB-treatment after discharge on complications including hepatic decompensation and mortality during 1-year follow-up, employing multivariable competing-risk-analyses. In a prospective cohort including 45 patients, we performed a comprehensive analysis of SI analysing 48 soluble inflammatory markers (SIMs) at baseline plus 3 and 6 months after TIPS-insertion. Overall, 175 (57.4%) patients received NSBB-therapy prior to TIPS-insertion; upon discharge, this decreased to 131 (22.9%), with 36 (27.5%) discontinuing NSBB within 1-year follow-up. Neither NSBB-therapy at TIPS-insertion nor treatment-continuation after discharge were associated with lower risks for hepatic decompensation, individual cirrhosis-associated complications or mortality neither in the periinterventional period nor during follow-up. Similarly, in the prospective cohort NSBB-intake was not linked to lower levels or a more prominent change of WBC, CRP or any other SIM at any of the investigated time points. NSBB-therapy at the time of TIPS-insertion and its (dis-)continuation afterwards seems to have no significant impact on SI, development of hepatic decompensation and survival.

Serum liver fibrosis markers predict hepatic decompensation in compensated cirrhosis

Background and aimThe literature is sparse on the association between serum liver fibrosis markers and the development of hepatic decompensation in patients with compensated cirrhosis. We aimed to assessed whether the serum liver fibrosis markers are predictive of the occurrence of hepatic decompensation.MethodsWe ascertained 688 cirrhotic patients with varying etiologies, between December 2015 to December 2019. Serum hyaluronic acid (HA), laminin (LN), collagen IV (CIV), and N-terminal propeptide of type III collagen (PIIINP) levels were measured at enrollment. All subjects were followed for at least 6 months for occurrence of hepatic decompensation. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of hepatic decompensation during follow-up.ResultsDuring a median follow-up of 22.0 (13.0–32.0) months, decompensation occurred in 69 (10.0%) patients. Multivariate analysis indicated that higher LN (HR: 1.008, 95% confidence interval [CI]: 1.002–1.014, P = 0.011) and CIV (HR: 1.004, 95% CI: 1.001–1.007, P = 0.003) levels were independently associated with hepatic decompensation. Furthermore, patients in the tertile 2 and tertile 3 groups for CIV levels had HRs of 4.787 (1.419, 16.152) (P = 0.012) and 5.153 (1.508, 17.604) (P = 0.009), respectively, for occurrence of decompensation event compared with those in the tertile 1 group.ConclusionSerum liver fibrosis markers, particularly in CIV, appeared to be reliable biomarkers of disease progression and liver decompensation in patients with compensated cirrhosis with varying etiologies.

Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis

Data are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed to assess the risk of hepatic decompensation in people with NAFLD with and without type 2 diabetes. We did a meta-analysis of individual participant-level data from six cohorts in the USA, Japan, and Turkey. Included participants had magnetic resonance elastography between Feb 27, 2007, and June 4, 2021. Eligible studies included those with liver fibrosis characterisation by magnetic resonance elastography, longitudinal assessment for hepatic decompensation and death, and included adult patients (aged ≥18 years) with NAFLD, for whom data were available regarding the presence of type 2 diabetes at baseline. The primary outcome was hepatic decompensation, defined as ascites, hepatic encephalopathy, or variceal bleeding. The secondary outcome was the development of hepatocellular carcinoma. We used competing risk regression using the Fine and Gray subdistribution hazard ratio (sHR) to compare the likelihood of hepatic decompensation in participants with and without type 2 diabetes. Death without hepatic decompensation was a competing event. Data for 2016 participants (736 with type 2 diabetes; 1280 without type 2 diabetes) from six cohorts were included in this analysis. 1074 (53%) of 2016 participants were female with a mean age of 57·8 years (SD 14·2) years and BMI of 31·3 kg/m2 (SD 7·4). Among 1737 participants (602 with type 2 diabetes and 1135 without type 2 diabetes) with available longitudinal data, 105 participants developed hepatic decompensation over a median follow-up time of 2·8 years (IQR 1·4-5·5). Participants with type 2 diabetes had a significantly higher risk of hepatic decompensation at 1 year (3·37% [95% CI 2·10-5·11] vs 1·07% [0·57-1·86]), 3 years (7·49% [5·36-10·08] vs 2·92% [1·92-4·25]), and 5 years (13·85% [10·43-17·75] vs 3·95% [2·67-5·60]) than participants without type 2 diabetes (p<0·0001). After adjustment for multiple confounders (age, BMI, and race), type 2 diabetes (sHR 2·15 [95% CI 1·39-3·34]; p=0·0006) and glycated haemoglobin (1·31 [95% CI 1·10-1·55]; p=0·0019) were independent predictors of hepatic decompensation. The association between type 2 diabetes and hepatic decompensation remained consistent after adjustment for baseline liver stiffness determined by magnetic resonance elastography. Over a median follow-up of 2·9 years (IQR 1·4-5·7), 22 of 1802 participants analysed (18 of 639 with type 2 diabetes and four of 1163 without type 2 diabetes) developed incident hepatocellular carcinoma. The risk of incident hepatocellular carcinoma was higher in those with type 2 diabetes at 1 year (1·34% [95% CI 0·64-2·54] vs 0·09% [0·01-0·50], 3 years (2·44% [1·36-4·05] vs 0·21% [0·04-0·73]), and 5 years (3·68% [2·18-5·77] vs 0·44% [0·11-1·33]) than in those without type 2 diabetes (p<0·0001). Type 2 diabetes was an independent predictor of hepatocellular carcinoma development (sHR 5·34 [1·67-17·09]; p=0·0048). Among people with NAFLD, the presence of type 2 diabetes is associated with a significantly higher risk of hepatic decompensation and hepatocellular carcinoma. National Institute of Diabetes and Digestive and Kidney Diseases.

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR.

Genetic variants including PNPLA3-rs738409 C>G, TM6SF2-rs58542926 C>T, MBOAT7-rs641738 C>T, and HSD17B13-rs72613567 T>TA have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the PNPLA3 minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the PNPLA3 G-allele in the overall cohort. Finally, carriage of PNPLA3 G-allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure.

Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study.

Background:There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD.Methods:Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality.Results:Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64–1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55–2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68–2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13–1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29–2.30, p = 0.71).Conclusions:Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy.

Management of portal hypertension severe complications

Portal hypertension is a clinical syndrome characterized by an increase in the portal pressure gradient, defined as the gradient between the portal vein at the site downstream of the site of obstruction and the inferior vena cava. The most frequent cause of portal hypertension is cirrhosis. In patients with cirrhosis, portal hypertension is the main driver of cirrhosis progression and development of hepatic decompensation (ascites, variceal hemorrhage, and hepatic encephalopathy), which defines the transition from compensated to decompensated stage. In decompensated patients, treatments aim at lowering the risk of death by preventing further decompensation and/or development of acute-on-chronic liver failure. Decompensated patients often pose a complex challenge which typically requires a multidisciplinary approach. The aims of the present review are to discuss the current knowledge regarding interventional treatments for patients with portal hypertension complications as well as to highlight useful information to aid hepatologists in their clinical practice. Specifically, we discuss indications and contraindications of transjugular intra-hepatic portosystemic shunt (TIPS) and balloon-occluded transvenous retrograde obliteration (BRTO) for the treatment of gastro-esophageal variceal hemorrhage in patients with decompensated cirrhosis (first section), we review the use of interventional treatments in patients with hepatic vein obstruction (Budd-Chiari syndrome) and in those with portal vein thrombosis (second section), and we briefly comment on the most frequent applications of selective splenic embolization in patients with and without underlying cirrhosis (third section).

Management of portal hypertension severe complications.

Portal hypertension is a clinical syndrome characterized by an increase in the portal pressure gradient, defined as the gradient between the portal vein at the site downstream of the site of obstruction and the inferior vena cava. The most frequent cause of portal hypertension is cirrhosis. In patients with cirrhosis, portal hypertension is the main driver of cirrhosis progression and development of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy), which defines the transition from compensated to decompensated stage. In decompensated patients, treatments aim at lowering the risk of death by preventing further decompensation and/or development of acute-on-chronic liver failure. Decompensated patients often pose a complex challenge which typically requires a multidisciplinary approach. The aims of the present review were to discuss the current knowledge regarding interventional treatments for patients with portal hypertension complications as well as to highlight useful information to aid hepatologists in their clinical practice. Specifically, we discussed the indications and contraindications of transjugular intra-hepatic portosystemic shunt and for the treatment of gastro-esophageal variceal hemorrhage in patients with decompensated cirrhosis (first section); we reviewed the use of interventional treatments in patients with hepatic vein obstruction (Budd-Chiari Syndrome) and in those with portal vein thrombosis (second section); and we briefly comment on the most frequent applications of selective splenic embolization in patients with and without underlying cirrhosis (third section).

Predictive value &amp;changes in Child-Pugh score in chronic hepatitis C cirrhotic patients treated with Direct Acting Antiviral agents

Background: Hepatitis C is a worldwide problem with a prevalence estimated to be 3 % according to the World Health Organization (WHO) about 130-150 million people worldwide are chronically infected with hepatitis C virus (HCV). Egypt has the highest prevalence of HCV estimated to be 7.3% with predominance of genotype 4. Direct -acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. The availability of antiviral agents, which can be administered in short, interferon (IFN)‐free regimens, has improved the management of patients with HCV infection dramatically. Clinical studies have demonstrated rates of sustained virologic response (SVR) of over 90% with these regimens, even in patients with compensated cirrhosis. Aim: The aim was to assess the clinical impact of direct-acting antiviral treatment in patients with compensated hepatitis C virus-related cirrhosis after one year of follow-up. Methods: An observational prospective study was conducted on 100 patients with compensated cirrhosis treated in 2017, analyzing the evolution of liver function and the development of hepatocellular carcinoma and clinical decompensation. Results: Most patients were males (60%), the mean age was 57.3±6.1years. All participants were Child-Pugh A class at the start of the treatment. SVR 12 was achieved in all patients (100%). Eight patients suffered clinical decompensation, three( 3.3%) of them changed to Child B and five (5.5%) patients changed to Child C. The incidence of de novo hepatocellular carcinoma during the follow-up was (4 %). There was a significant improvement in the mean platelets count, AST, ALT (P < 0.001) after treatment and the mean albumin level decreased but still in the normal range. Conclusion: Treatment with Direct-acting antiviral was assosciated with high rates of SVR, but not associated in the short term with a decrease in the development of hepatic decompensation or hepatocellular carcinoma compared to what it was reported for untreated compensated cirrhotic patients.

Changes in Liver Stiffness, Measured by Magnetic Resonance Elastography, Associated With Hepatic Decompensation in Patients With Primary Sclerosing Cholangitis

Single measurements of liver stiffness (LS) by magnetic resonance elastography (MRE) have been associated with outcomes of patients with primary sclerosing cholangitis (PSC), but the significance of changes in LS over time are unclear. We investigated associations between changes in LS measurement and progression of PSC. We performed a retrospective review of 204 patients with patients who underwent 2 MREs at a single center between January 1, 2007 and December 31, 2018. We collected laboratory data and information on revised Mayo PSC risk and model for end-stage liver disease scores, the PSC risk estimate tool, and levels of aspartate transferase at the time of each MRE. The ΔLS/time was determined by the change in LS between the second MRE compared to the first MRE divided by the time between examinations. The primary endpoint was development of hepatic decompensation (ascites, variceal hemorrhage or hepatic encephalopathy). The median LS measurement was 2.72 kPa (interquartile range, 2.32-3.44 kPa) and the overall change in LS was 0.05 kPa/y. However, ΔLS/y was 10-fold higher in patients anticipated to have cirrhosis (0.31 kPa/y) compared to patients with no fibrosis (0.03 kPa/y). The median LS increased over time in patients who ultimately developed hepatic decompensation (0.60 kPa/y; interquartile range, 0.21-1.26 kPa/y) vs but remained static in patients who did not (reduction of 0.04/y; interquartile range, reductions of 0.26 to 0.17 kPa/y) (P < .001). The ΔLS/y value associated with the highest risk of hepatic decompensation was Δ0.34 kPa/y (hazard ratio [HR], 13.29; 95% CI, 0.23-33.78). After we adjusted for baseline LS and other risk factors, including serum level of alkaline phosphatase and the Mayo PSC risk score, ΔLS/y continued to be associated with hepatic decompensation. The optimal single LS cut-off associated with the hepatic decompensation was 4.32 kPa (HR, 60.41; 95% CI, 17.85-204.47). A combination of both cut-off values was associated with risk of hepatic decompensation (concordance score, 0.93; 95% CI, 0.88-0.98) CONCLUSIONS: A single LS measurement and changes in LS over time are independently associated with hepatic decompensation in patients with PSC. However, changes in LS occur slowly in patients without advanced fibrosis or hepatic decompensation.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy.

Background and AimsSustained virologic response (SVR) to interferon (IFN)‐free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN‐free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH.Approach and ResultsThe study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow‐up [FU]) IFN‐free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08‐1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC], < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86‐0.92) in most patients, especially if assessed in a sequential manner.ConclusionsReassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An “immediate” HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.

Weight Loss Through Bariatric Surgery Is Associated With Lower Rates of Hepatic Decompensation

Introduction: The obesity epidemic has not spared patients with cirrhosis. Obesity has been shown to increase the probability of clinical decompensation independent of portal pressure or hepatic synthetic function. Various modalities of weight reduction have emerged as therapeutic targets in the management of cirrhosis regardless of etiology. Bariatric surgery has become the gold standard treatment for morbid obesity, with data suggesting bariatric surgery is safe and effective in patients with compensated cirrhosis. This study aimed to explore the relationship between weight reduction surgery and the development of hepatic decompensation. Methods: Fourteen biopsy-proven patients with cirrhosis who underwent bariatric surgery (cases) at our institution from 1/1/2000-6/31/2017 were identified using diagnosis and procedural codes. A retrospective chart review was utilized to validate coded diagnoses. Twenty-eight controls were selected from a database of patients with cirrhosis and obesity and matched for body mass index (BMI), age, and metabolic syndrome components. The prevalence of hepatic decompensation in relation to BMI was compared between groups. Results: There were no statistically significant differences in demographic characteristics between the groups including age, sex, race, metabolic syndrome components, or etiology of cirrhosis; though 93% of cases had NASH cirrhosis (Table 1). All cases (n=14) had compensated cirrhosis at the time of surgery, and no cases developed hepatic decompensation. Average pre-surgery BMI was 50.4 kg/m2compared to 38.7 kg/m2at the end of follow-up (average decrease in BMI of 12.1 kg/m2in cases). In contrast, 54% of controls were diagnosed with decompensated cirrhosis. Average BMI at the time of clinical decompensation in controls was 44.6 kg/m2. The difference in BMI between cases (38.7 kg/m2)and all controls (45.3 kg/m2) reached statistical significance (p=0.01), as did the difference in BMI between cases (38.7 kg/m2) and controls with decompensation (44.6 kg/m2; p=0.04). Conclusion: Bariatric surgery in patients with cirrhosis resulted in a decrease in BMI without clinical decompensation. In a control group of obese patients with cirrhosis matched for age and metabolic syndrome components, decompensation was diagnosed in 54% during the study period. These results support prior data suggesting weight loss may be associated with decreased rates of clinical decompensation in patients with cirrhosis.958 Figure 1 No Caption available.

Prognostic Role of Liver Stiffness Measurements Using Magnetic Resonance Elastography in Patients with Compensated Chronic Liver Disease.

To retrospectively evaluate the prognostic role of liver stiffness (LS) measurement using magnetic resonance elastography (MRE) in patients with compensated chronic liver disease (cCLD). We enrolled 217 patients with cCLD who underwent MRE. After mean follow-up of 45.0 ± 17.6 months, cumulative incidence (CI) of hepatocellular carcinoma (HCC) occurrence, development of decompensation and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazard regression model. During the follow-up period, HCC occurred in 33 patients, and 1-, 3- and 5-year CIs of HCC occurrence were 3.8%, 14.8% and 18.9%, respectively. The LS value was a significant predictive factor for HCC occurrence [p < 0.001, hazard ratio (HR) = 1.59 per unit (1.25-2.03)]. Eighteen patients experienced hepatic decompensation, and 1-, 3- and 5-year CIs of decompensation were 2.8%, 7.3% and 11.3%, respectively. The LS value was also significantly associated with decompensation development [p < 0.001, HR = 2.02 per unit (1.37-2.98)]. Fourteen patients died, and 1-, 3- and 5-year OSs were 99.1%, 98.0% and 89.8%, respectively. The LS value was demonstrated to be a significant affecting factor for OS [p = 0.008, HR = 1.39 per unit (1.10-1.78)]. LS obtained from MRE was a significant predictive factor for the development of decompensation, HCC occurrence and OS in cCLD patients. • Liver stiffness (LS) values obtained from MRE can provide prognostic information. • The LS value was a significant predictive factor for occurrence of hepatocellular carcinoma. • The LS value was significantly associated with development of hepatic decompensation. • Survival of compensated chronic liver disease patients was affected by the LS value.

Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis.

Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD. We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies. We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding. Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

Quantitative Liver Function Analysis: Volumetric T1 Mapping with Fast Multisection B1 Inhomogeneity Correction in Hepatocyte-specific Contrast-enhanced Liver MR Imaging.

Purpose To determine whether B1 inhomogeneity-corrected volumetric T1 maps of gadoxetic acid-enhanced liver magnetic resonance (MR) imaging are able to demonstrate global liver function and functional heterogeneity in patients with cirrhosis and to investigate their relationship with the development of hepatic insufficiency and decompensation. Materials and Methods This institutional review board-approved retrospective study with waiver of informed consent included 234 consecutive patients who underwent gadoxetic acid-enhanced liver MR imaging, including B1 inhomogeneity-corrected volumetric T1 mapping. For all patients, T1 relaxation times of the liver and liver volumes were measured on T1 maps. Liver T1 and functional liver volume-to-weight ratio (liver volume divided by liver T1 and the patient's weight) were compared between Child-Pugh class A and class B cirrhosis. Associations between serum markers, MR parameters, hepatic insufficiency, and decompensation were investigated by using Cox proportional hazards analysis. Results Patients with Child-Pugh class B disease showed significantly longer liver T1 (548.2 msec ± 257.7 vs 372.2 msec ± 77.5, P < .0001) and lower kurtosis of liver T1 (29.1 ± 39.6 vs 43.9 ± 64.9, P = .016) than patients with Child-Pugh class A disease. Prolonged liver T1 (≥462 msec) (hazard ratio [HR], 5.9; 95% confidence interval [CI]: 1.1, 62.8) and an albumin level of less than 3.5 g/dL (HR, 20.7; 95% CI: 3.9, 221.9) were independently associated with the development of hepatic insufficiency. Functional liver volume-to-weight ratio was associated with the development of hepatic decompensation in patients with Child-Pugh class A disease (HR, 0.03; 95% CI: 0.004, 0.23). Conclusion B1 inhomogeneity-corrected volumetric T1 mapping provided information on global liver function and demonstrated functional heterogeneity. In addition, prolonged liver T1 (≥462 msec) was associated with the development of hepatic insufficiency, and functional liver volume-to-weight ratio was negatively related with the development of decompensation in compensated cirrhosis. © RSNA, 2016 Online supplemental material is available for this article.

Impact of therapy on the outcome of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is a dynamic state in which HBV replication is the key driving force of disease progression, resulting in the development of hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC). The primary aim of therapy is to eliminate or suppress HBV to reduce the activity of hepatitis thus reducing the risk of or slowing the progression of liver disease. Treatment with nucleos(t)ide analogues (Nuc) may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function thus increasing survival in patients with hepatic decompensation. The long-term benefits of a finite course of interferon α (IFN) therapy include a sustained and cumulative response, as well as a reduction in the progression of fibrosis and in the development of cirrhosis and/or HCC. Long-term Nuc therapy may also result in histological improvement or reversal of advanced fibrosis and reduction in disease progression including the development of HCC. Hepatitis B surface antigen (HBsAg) seroclearance, a status close to a "cure", may also occur in patients with a sustained or maintained viral response, especially in those with IFN-based therapy. Pegylated IFN (PEG-IFN) and newer Nucs may have even better long-term outcomes because of improved efficacy and/or a low risk of drug resistance. However, treatment outcomes are still far from satisfactory. The development of more effective and safe but affordable anti-HBV agents/strategies is needed to further improve outcomes.

Sa1008 Interleukin-28b (IL-28B) Polymorphism Has No Impact on the Long-Term Outcome of Patients With HCV-Related Cirrhosis: A 15-Years Retrospective-Prospective Cohort Study

Background: Whether IL-28B polymorphism modulates the outcome of patients with HCVrelated cirrhosis remains unknown. Aim: to assess the effect of IL-28B polymorphism on the long-term course of patients with cirrhosis carrying HCV infection. Methods: IL-28B region (rs1297860) SNP was retrospectively determined by real-time PCR on DNA extracted from frozen blood EDTA or paraffin-embedded liver tissue. Differences in baseline demographical, virological, and clinical features of patients according to IL-28B genotype was assessed by the Student T, Fisher's exact andMantel-Haenszel tests respectively for continuous categorical and ordinal variables. Results:IL-28B genotype determinationwas available for 213 (45%)of all consecutive HCV-infected patients with either compensated or decompensated cirrhosis (Child class C excluded) enrolled in a prospective long-term follow-up study (53% males, mean age 57±8,5 years, 63% genotype 1, 55% received antiviral therapy, 26% attained sustained virological response (SVR). Overall, the frequency of CC, CT and TT genotype was 34%, 53% and 13%, with no difference between compensated or decompensated patients, at entry. CC genotype was observed in 24% of patients infected with HCV genotype 1 compared to 51% of subjects infected with other genotypes (P<0.0001). SVR was achieved in 51% of patients with CC genotype compared to 13% and 6% in those with CT and TT genotype, respectively (p<0.0001). IL-28B and SVR remained independently associated after adjustment for HCV genotype (p=0.003). Among the 85 treated patients without previous decompensation who did not achieve SVR, no association was found between IL-28B and development of hepatic decompensation, hepatocellular carcinoma and death after a median follow-up of 15 years Conclusion: The present study shows that IL-28B genotype has no impact on the outcome of patients with HCV-related cirrhosis. These results also confirm that, irrespective of genotype, IL-28B CC polymorphism is associated with the likelihood to achieve SVR and with non-1 HCV genotype infection.

Sa1010 Outcomes and Safety of Open vs. Laparoscopic Surgery in Patients With Cirrhosis

Background: Whether IL-28B polymorphism modulates the outcome of patients with HCVrelated cirrhosis remains unknown. Aim: to assess the effect of IL-28B polymorphism on the long-term course of patients with cirrhosis carrying HCV infection. Methods: IL-28B region (rs1297860) SNP was retrospectively determined by real-time PCR on DNA extracted from frozen blood EDTA or paraffin-embedded liver tissue. Differences in baseline demographical, virological, and clinical features of patients according to IL-28B genotype was assessed by the Student T, Fisher's exact andMantel-Haenszel tests respectively for continuous categorical and ordinal variables. Results:IL-28B genotype determinationwas available for 213 (45%)of all consecutive HCV-infected patients with either compensated or decompensated cirrhosis (Child class C excluded) enrolled in a prospective long-term follow-up study (53% males, mean age 57±8,5 years, 63% genotype 1, 55% received antiviral therapy, 26% attained sustained virological response (SVR). Overall, the frequency of CC, CT and TT genotype was 34%, 53% and 13%, with no difference between compensated or decompensated patients, at entry. CC genotype was observed in 24% of patients infected with HCV genotype 1 compared to 51% of subjects infected with other genotypes (P<0.0001). SVR was achieved in 51% of patients with CC genotype compared to 13% and 6% in those with CT and TT genotype, respectively (p<0.0001). IL-28B and SVR remained independently associated after adjustment for HCV genotype (p=0.003). Among the 85 treated patients without previous decompensation who did not achieve SVR, no association was found between IL-28B and development of hepatic decompensation, hepatocellular carcinoma and death after a median follow-up of 15 years Conclusion: The present study shows that IL-28B genotype has no impact on the outcome of patients with HCV-related cirrhosis. These results also confirm that, irrespective of genotype, IL-28B CC polymorphism is associated with the likelihood to achieve SVR and with non-1 HCV genotype infection.

Goals of therapy in patients with CHB

Despite the development of a number of antiviral agents for treatment of Chronic Hepatitis B, the treatment of chronic hepatitis B continues to be a challenge for physicians due to the high burden of the disease and the limited efficacy of available therapy. The primary goal of treatment is to eliminate or suppress HBV in order to decrease pathogenicity and infectivity, and reduce hepatic necroinflammation. Clinically, the short-term goal of treatment is to reduce hepatic activity, to prevent the development of hepatic decompensation, to ensure loss of HBeAg (with seroconversion to anti-HBe) and/or HBV-DNA with alanine aminotransferase (ALT) normalization at the end or 6-12 months after the end of treatment. The long-term goals are eradication of infection, prevent progression to cirrhosis, prevent development of HCC, and ultimately prolong survival. This review discusses the goals of therapy in patients with chronic hepatitis B.

Viral hepatitis

Viral hepatitis affects millions of people worldwide, making it one of the most important diseases in the field of hepatology. The response to the hepatitis A vaccine is optimal when targeted to patients with chronic hepatitis before development of hepatic decompensation. A new triple antigen vaccine for hepatitis B virus produces a greater degree of protection. Lamivudine can achieve a 3-to 4-log reduction in serum viral levels in patients with chronic hepatitis B infection. Lamivudine-resistant mutants appear in more than 50% of patients after prolonged treatment. Entecavir can be given safely for a short time and causes a pronounced reduction in hepatitis B viral DNA levels with slower rebound after stopping therapy than has been reported with lamivudine. Pegylated interferon has sustained absorption, a slower rate of clearance and a longer half-life than unmodified interferon alfa. Pegylated interferon alfa-2a administered once weekly is more effective than standard interferon alfa-2a administered three times weekly. In patients with chronic hepatitis C infection, the most effective therapy is the combination of pegylated interferon plus ribavirin. Other major advances in the field of viral hepatitis during the past year are highlighted.

Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients

Hepatitis A virus (HAV) vaccination is recommended in chronic liver disease because of an increased morbidity and mortality associated with HAV superinfection. However, data regarding the efficacy of HAV vaccination in patients with advanced chronic liver disease is limited. We assessed the efficacy of a standard HAV vaccination schedule in decompensated chronic liver disease in comparison with compensated disease and defined clinical predictors associated with seroconversion. Eighty-four anti-HAV antibody–negative patients, 49 with compensated liver disease, and 35 with decompensated disease were enrolled. Seroconversion was measured by qualitative and quantitative anti-HAV antibody measurements 1 month after each vaccine dose, and univariate/multivariate analysis was performed to define clinical predictors associated with seroconversion. One month after the primary dose, 71.4% of patients with compensated liver disease had detectable anti-HAV antibody compared with 37.1% with decompensated liver disease (P < .05). One month after the booster dose, 98% of compensated patients seroconverted compared with 65.7% with decompensated disease (P < .05). The median serum antibody concentration in compensated liver disease was 76.4 mIU/mL at month 1 and 327.91 mIU/mL at month 7 compared with 20.0 mIU/mL and 102.57 mIU/mL, respectively, in decompensated disease. On multivariate analysis, Child-Pugh class was the only factor predicting response to vaccination. Seroconversion after HAV vaccination was significantly less common in decompensated liver disease and the presence of advanced disease (Child-Pugh class B/C) predicted a lower response rate. These findings indicate that the response to HAV vaccination in chronic liver disease is optimal when targeted to patients before the development of hepatic decompensation. (HEPATOLOGY 2001;34:28-31.)