Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Hofer, Benedikt; Simbrunner, Benedikt; Hartl, Lukas; Jachs, Mathias; Bauer, Dávid; Balcar, Lorenz; Paternostro, Rafael; Schwabl, Philipp; Semmler, Georg; Scheiner, Bernhard; Staettermayer, A.F.; Trauner, Michael; Mandorfer, Mattias; Reiberger, T

doi:10.1016/j.cgh.2022.11.033

Cited by 52 publications

(34 citation statements)

References 22 publications

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“…Although alcohol abstinence itself has previously been shown to improve prognosis, even in decompensated patients, 7,8,10 implications of clinical improvements upon abstinence in alcohol‐related cirrhosis remain poorly understood and the potential to achieve hepatic recompensation according to Baveno VII criteria has not yet been investigated. In a landmark study by Vorobioff et al, 16 patients with cirrhosis due to ALD who abstained from alcohol demonstrated significant improvements in portal pressure and Child‐Pugh score, which translated into an improved survival.…”

Section: Discussionmentioning

confidence: 99%

“…The cumulative incidence of recompensation was 9.0% at 1 year, 16.3% at 2 years and 17.7% at 3 years (Figure 1A). At baseline, patients who recompensated during follow-up demonstrated a significantly lower Child-Pugh score (7 [6-9] vs. 8 [7][8][9][10]) and HVPG (19 [17-21] vs. 21 [18][19][20][21][22][23][24] mmHg), as well as a higher mean arterial pressure (MAP) (101 [94-108] vs. 94 [86-104] mmHg) when compared with patients who remained decompensated (Table 1). With regard to abstinence duration, we observed no significant difference between patients who eventually recompensated (6.…”

Section: Hepatic Recompensationmentioning

confidence: 99%

“…4,5 Key pathophysiological drivers of decompensation and disease progression in ALD are the development of portal hypertension and continued alcohol consumption. [6][7][8][9][10] However, despite ongoing research efforts, pharmacotherapy of portal hypertension and cirrhosis in ALD is still limited to non-selective betablockers (NSBBs), which decrease portal pressure and reduce systemic inflammation. [11][12][13] In light of this limited repertoire of pharmacological options, curing the underlying aetiology of alcohol-related cirrhosis, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Overall, future prospectively designed studies are required to fully elucidate the natural history of hepatic recompensation, investigate the probability of recompensation in patients with to AAH or ACLF and explore modifying factors. Importantly, the future analysis of potential noninvasive biomarkers may enable the early identification of patients who are likely to achieve significant improvements following abstinence, thus facilitating individualised patient care.Although alcohol abstinence itself has previously been shown to improve prognosis, even in decompensated patients,7,8,10 implications of clinical improvements upon abstinence in alcohol-related cirrhosis remain poorly understood and the potential to achieve hepatic recompensation according to Baveno VII criteria has not yet been investigated. In a landmark study by Vorobioff et al, 16 patients with cirrhosis due to ALD who abstained from alcohol demonstrated significant improvements in portal pressure and Child-Pugh score, which translated into an improved survival.…”

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confidence: 99%

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Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol‐related cirrhosis

Hofer

Simbrunner

Hartl

et al. 2023

Liver International

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Background & AimsRemoving the primary aetiological factor in decompensated cirrhosis may lead to a restoration of hepatic function. In this study, we investigated the clinical implications of recompensation and the subsequent survival in patients with decompensated alcohol‐related cirrhosis.MethodsThe rate of recompensation was evaluated in patients with decompensated alcohol‐related cirrhosis and persistent alcohol abstinence undergoing a hepatic venous pressure gradient (HVPG) measurement. Recompensation was defined according to Baveno VII criteria as resolution of ascites and hepatic encephalopathy, absence of variceal bleeding and improvement in liver function.ResultsTwo hundred and four abstinent patients with decompensated alcohol‐related cirrhosis (age: 57.2 [IQR:50.1–63.7] years; 75.0% male; median MELD: 15 [IQR:11–19]) and a median HVPG of 20 (IQR:18–24) mmHg were included. During a median follow‐up of 24.4 (IQR:10.9–50.4) months, 37 patients (18.1%) achieved abstinence‐induced recompensation. Lower baseline HVPG, lower Child‐Pugh score, lower BMI, higher albumin and higher mean arterial pressure were linked to a higher probability of recompensation. After adjusting for age, disease severity, portal hypertension and systemic inflammation, achieving recompensation resulted in a significant and considerable reduction in liver‐related mortality (adjusted HR: 0.091 [95% CI: 0.012–0.677]; p = .019). Only 13 patients (6.4%) developed hepatocellular carcinoma, with a tendency towards a lower risk upon recompensation (HR: 0.398 [95% CI: 0.084–1.878]; p = .245), yet this finding did not reach statistical significance and requires further investigation.ConclusionsAlcohol abstinence led to recompensation in 18.1% of our cohort of HVPG‐characterised patients with decompensated alcohol‐related cirrhosis. Achieving hepatic recompensation resulted in a >90% risk reduction in liver‐related mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Hepatic Recompensationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol‐related cirrhosis

Hofer

Simbrunner

Hartl

et al. 2023

Liver International

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“…A study found that, in patients who were alive 6 months after the episode of severe alcoholic hepatitis, alcohol abstinence along with the Lille response were the only significant predictors of the long‐term outcome (hazard ratio, 3.9; P < 0.0001) 27 . In another retrospective study with prospective follow‐up of 320 patients with alcohol‐related cirrhosis, only abstinence and age were found to be significant predictors of liver‐related mortality 28 . Interestingly, the MELD score and hepatic venous pressure gradient measured at baseline were no longer significant predictors when they were adjusted for amount of alcohol intake 28 …”

Section: Current Treatment Optionsmentioning

confidence: 99%

Current and future treatment for alcoholic‐related liver diseases

Yoon

Kim

2023

J of Gastro and Hepatol

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The socioeconomic burden of alcohol-related liver disease has been increasing worldwide. Its prevalence is underestimated, and patients with alcohol-related liver disease are rarely diagnosed in the earlier phase of the disease spectrum. Alcoholic hepatitis is a distinct syndrome with life-threatening signs of systemic inflammation. In severe alcoholic hepatitis, prednisolone is indicated as the first-line treatment even with the possibility of various complications. Early liver transplantation can be another option for highly selected patients with a null response to prednisolone. Most importantly, abstinence is the mainstay of long-term care, but relapse is frequent among patients. Recent findings on the pathogenesis of alcoholic hepatitis have enabled us to discover new therapeutic targets. Preventing hepatic inflammation, reducing oxidative stress, improving gut dysbiosis, and enhancing liver regeneration are the main targets of emerging therapies. Herein, we review the pathogenesis, current treatment, and barriers to successful clinical trials of alcoholic hepatitis. Additionally, clinical trials for alcoholic hepatitis, either ongoing or recently completed, will be briefly introduced.

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Inflammation remains a dynamic component of portal hypertension in regressive alcohol‐related cirrhosis

Hofer,

Simbrunner,

Königshofer

et al. 2024

UEG Journal

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BackgroundPortal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver‐related complications even after removing the underlying aetiological factor.ObjectiveWe investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin‐induced cirrhosis and patients with alcohol‐related cirrhosis.MethodsIn mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin‐withdrawal allowing for one or 2 weeks of regression. Furthermore, 128 patients with alcohol‐related cirrhosis and alcohol abstinence undergoing same‐day hepatic venous pressure gradient (HVPG) and liver stiffness measurement (LSM) were included. The influence of inflammation on the dynamic PH component was assessed using linear models. Specifically, we explored proinflammatory changes in mice/patients in whom the measured portal pressure (PP)/HVPG was significantly higher than the PP/HVPG expected from the static PH component (histological collagen proportionate area [CPA; %] in mice, LSM in patients).ResultsIn mice, toxin discontinuation induced a significant decrease in PP, CPA, histological hepatic inflammation and hepatic expression of proinflammatory genes (Tnfa, Il6, Cxcl1, Mcp1; all p < 0.05 for one/2 week regression vs. peak disease). Similarly, prolonged abstinence in alcohol‐related cirrhosis was linked to lower HVPG/LSM and longer abstinence was correlated to lower C‐reactive protein (CRP), IL‐6, immunoglobulin A (IgA) and IgG levels (all p < 0.05). Nevertheless, the persistence of a low‐grade proinflammatory state during regression was linked to a higher PP/HVPG than expected from static PH components. In regressive mice, higher hepatic proinflammatory gene expression (Tnfa, Il6, Il1b; all p < 0.05) was linked to higher‐than‐expected PP. Similarly, higher CRP, IL‐6, IgA and IgG and lower complement factor C3c (all p < 0.05) were associated with higher‐than‐expected HVPG in abstinent patients with alcohol‐related cirrhosis.ConclusionsAlthough removing the underlying aetiological factor resulted in significant improvements, a persistent hepatic proinflammatory environment remained a key driver of the dynamic PH component in regressive liver disease.Clinical trial numberNCT03267615.

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Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Cited by 52 publications

References 22 publications

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol‐related cirrhosis

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol‐related cirrhosis

Current and future treatment for alcoholic‐related liver diseases

Inflammation remains a dynamic component of portal hypertension in regressive alcohol‐related cirrhosis

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