ACG Offers Guidelines for Acute-on-Chronic Liver Failure

Nancy S. Reau, MD


March 07, 2022

Chronic liver disease is a mounting problem worldwide, and one that is greatly compounded when combined with other precipitating events (eg, alcohol-related or viral hepatitis, drug-induced liver injury), which is termed acute-on-chronic liver failure (ACLF). Although ACLF has been described only relatively recently, it represents a significant contributor to mortality.

The American College of Gastroenterology (ACG) convened a team of experts with the goal of helping clinicians recognize and appropriately manage ACLF. This resulted in practice guidelines recently published in the American Journal of Gastroenterology.

To find out more about best practices surrounding ACLF, Medscape contributor Nancy S. Reau, MD, chief of the hepatology section at Rush University Medical Center in Chicago, spoke with the guidelines' lead author, Dr Jasmohan S. Bajaj, MD, MS, a professor of medicine in the Division of Gastroenterology, Hepatology, and Nutrition at Virginia Commonwealth University and Richmond VA Medical Center in Richmond, Virginia.

Addressing an Unmet Need for ACLF Education

Why was it important to offer guidelines for ACLF?

We believe the time was prime to move the needle forward and raise awareness, among not only hepatologists and intensive care unit (ICU) specialists but also the general gastrointestinal audience who may or may not deal with cirrhosis or will be dealing with chronic liver disease in the future.

The guidelines provide an expansive view of ACLF as it's been increasingly diagnosed throughout the world. There's something in here for everyone, regardless of which part of the globe you're in.

These guidelines begin by addressing the difficulty in even defining ACLF. Why has that been such a challenge?

In part because the liver disease severity we see at baseline is different around the world. For example, in Asia, there could be patients with chronic liver disease who have a hepatitis B flare — which would also be ACLF because the definitions are chronic liver disease, not just cirrhosis. Whereas in the West, it's cirrhosis plus infection. Some guidelines did not include infection as a precipitant of ACLF, whereas others did.

It's a little difficult to thread this needle, but we hope we've done it, because ACLF is clearly a distinct entity from acute decompensation, and it has a much worse prognosis. Even if you take out all the minutiae of the guidelines, it's largely characterized by liver failure plus a few extrahepatic organ failures. If unreversed or untreated, it will result in death.

That's definitely a simpler message than many of the other ways of trying to define ACLF.

A Tool for Identifying ACLF

You provide a flowchart in the guidelines that walks clinicians through key decision-making. As you said, a patient with ACLF has a really high chance of dying; but, if you have a patient with multiorgan failure, this is not always going to be a patient where the answer is clearly transplant or treat with x. That tool helps a clinician understand what you can and can't improve, how to do that, and when to do that, which is probably life-saving.

I agree. A pragmatic approach to a patient who has chronic liver disease or cirrhosis, and now has completely gone into ACLF, is to try and do everything in your power to reverse that ACLF if possible. However, it's a bit like having a foot in two boats at the same time. You want to also make sure that these patients are transplant candidates, and if they are on the transplant list, that they continue to maintain their eligibility. But if they're not, and if they meet criteria for delisting, we also want to start the conversation with the patient — if they're awake — and their family members, relatively early. That helps to keep it from coming as a big shock when these things happen.

Obviously, we are dealing with very sick patients in the ICU setting, so this needs to be done in collaboration with our ICU and palliative care colleagues. It's another reason why hepatologists should also be, if not trained, at least familiar with the palliative care resources that are at their disposal and have at least a working knowledge of how to approach patients and their families in case this situation arises.

At my institution, our ICU is sometimes frustrated when they see a patient with a very prolonged course who is inevitably not going to do well. They strongly appreciate when the transplant service or the liver service gets involved early to help with the transition, so the family is aware.

That increased awareness among palliative care, ICU, and transplant coordinated services is going to eliminate a lot of frustration and help consistent messaging for families, if you're all on the same page.

Absolutely. It's a team sport.

Establishing a Process for Early Transplant

As you said, some patients need to be delisted because they suddenly become very sick. However, some might be patients with well-compensated cirrhosis with whom you hadn't even gotten around to talking to about transplant, and suddenly transplant is their best avenue. Do you have any suggestions on how to recognize that patient over others who are going to do poorly?

Because these guidelines are for a broader audience, the first step is to ensure that, if you are not a liver transplant center, you know where your closest liver transplant center is. Early in the process, when you know that the patient is not going to do well, call the liver transplant center. Because even when it's expedited, a typical liver transplant workup still needs all these i's dotted and t's crossed to make sure that the patient is the best candidate, will survive the surgery, and will have an acceptable quality of life and graft survival afterward.

We want to be vigilant. If the patient starts getting into ACLF territory, that's the time to reevaluate very carefully — either yourself or through your transplant team or an external center who has been instrumental in performing transplant in your patients. It must happen quickly to see whether this person could potentially be transferred under the care of someone, if they are transplant candidates.

For example, we work at one of the six VA transplant sites here. The VA system requires patients from all over the country to be evaluated or transferred to these six VA transplant centers. We do SCAN-ECHO (Specialty Care Access Network-Extension for Community Healthcare Outcomes) remotely in case someone needs our help and decide whether this patient needs to be transferred here or not. I'm sure that's also the case in your situation at Rush and other centers.

Long story short, if a patient is not doing well and you had not thought about transplant before, the soonest you can get in touch with someone who can guide you is the best way to manage this patient and give them a fighting chance.

As much as we sometimes criticize our VA care, this is one place where it is exceptional. You're an integrated service, and that ability to quickly triage and move patients is something other academic centers don't always do well.

Individual Considerations Based on Type of Organ Failure

The guidelines are granular, breaking down organ dysfunction by each organ system. Some of these are going to be much more intuitive and directed, and some of them are going to be harder because the degree of pathology is broadly spread. How would you help a clinician use these metrics?

Bajaj: It was very important to us that we went through each of these individually, because the only organ failure that is consistent across all guidelines is grade 3 and 4 hepatic encephalopathy as brain failure. Otherwise, there are varying definitions.

But the more organ failures a person has, the worse off they're going to be. You don't need to be a scientist to know this.

The important take-home points include not to rely on international normalized ratio for coagulation risk. It can be a measure of liver disease severity, but not something that would be a coagulation risk. When it comes to circulation, we obviously want to make sure that the patient is not in shock, and that is not unique to cirrhosis. It's the same with ventilation, where we want to make sure people follow best practices and avoid ventilator-associated pneumonia.

Patients with acute kidney injury can easily morph into kidney failure, defined either by stage 2 and 3 acute kidney injury or by a need for dialysis.

There is a nuance here regarding end-stage liver disease and dialysis. In patients with ACLF in whom you want to do dialysis, typically it's a judgement call, which is where the transplant center comes in. Do you want to put someone who is not a transplant candidate on dialysis just to improve their kidney function? Or is there something that can give this patient to extend their life before they get a transplant? As you know, if you are on dialysis, it improves your transplant suitability, as far as the listing criteria is concerned.

A decision you must make very carefully, in concert with your nephrologist, ICU care people, and the liver transplant team, is whether a patient who's slipping into ACLF and predominantly has renal issues should undergo dialysis at that stage or not. That is the big inflection point, because it's harder to stop dialysis once started rather than to not start at all in someone who is not a liver transplant candidate and is otherwise not going to do well, regardless of the dialysis.

This is a time when your nephrology colleagues are going to appreciate a tool that helps the patient, their family, and the hospital team have a conversation about the appropriateness of something that could be lifesaving and a bridge to transplant or could prolong the inevitable in a person who doesn't have those options. These tools are important as we look at the efficiency and cost of care.

Also, from a family standpoint, no one wants to have a process drawn out over 6 weeks where you knew the outcome at an earlier point in time.

Managing Clotting and Infections

The guidelines also address places where we probably don't do standard of care as well as we should, such as deep venous thrombosis (DVT) prophylaxis. How do you convince some of the co-managing teams that we should be doing something like subcutaneous heparin in a patient who looks like they might have an increased risk for bleeding but probably doesn't?

Different people practice differently, but clearly there's an increased risk for DVT in these patients. It may not be the usual DVT in the calf that we typically see. It could also be splanchnic or mesenteric thrombosis, which we worry about because the instability of the coagulation parameters in cirrhosis is very high. Anything can push them into bleeding or a clotting diathesis. We want to make sure that we don't help to exacerbate these situations, especially in the setting of infections.

If there's no contraindication, we do ask them to continue venous thromboembolism treatment.

We may want to start a checklist to prove that this is not the case. But prior studies have shown that they do not worsen bleeding outcomes in these patients and could potentially reduce the DVT, because many of these patients have sarcopenia, are deconditioned, and will probably stay in a supine or sitting position before they are either transplanted or get discharged.

Is there anything important in the guidelines that we didn't cover?

Infections are one of the most common precipitants of ACLF across Western countries. Even in Eastern countries, like many parts of India and China, infections have been one of the highest precipitants of ACLF or acute multiorgan failure.

We want to nip them in the bud because once ACLF has set in, it is very hard to control.

To do that, we want to identify infections promptly and make sure we give the broadest-spectrum antibiotic initially and then narrow it down. If the patient is not responding, you should have a very early suspicion and broaden that even more and add fungal coverage. For this, we need yet another person on the team: the infectious disease doctor, who should be involved in case the patient doesn't start responding.

In general, though, I would say that there are four key take-home points from these guidelines for general gastrointestinal practitioners:

  • This is different from acute decompensation;

  • It can happen against a background of chronic liver disease (F2 or higher) and not just cirrhosis;

  • It's important to notice infections early; and

  • You need to be in touch with your transplant person.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.

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