Does Leukemia Affect the Liver? Signs & Complications

Leukemia can affect the liver through several distinct routes, and it does so more often than many people realize. In one pediatric study, more than half of children diagnosed with certain types of acute leukemia already had detectable liver abnormalities at the time of their initial diagnosis. Beyond the disease itself physically infiltrating liver tissue, the treatments used to fight leukemia and the infections that exploit a weakened immune system can each take a separate toll on the organ. The result is a complicated picture where the liver sits at the intersection of the cancer, its therapy, and its side effects.

How Leukemia Cells Physically Invade the Liver

The liver is one of the most blood-rich organs in the body, and leukemia is a cancer of the blood. That combination creates a direct pathway for malignant cells to reach liver tissue. Research in animal models has shown that leukemia cells express specific chemical-signaling receptors that guide them toward the liver. In one mouse study, a receptor called Ccr1 was expressed at levels 149 times higher in leukemia cells invading the liver compared with normal immune cells found in healthy mouse livers.¹ In other words, the cancer cells are not arriving at the liver by accident. They carry molecular homing signals that pull them there.

Once leukemia cells reach the tiny blood vessels inside the liver (called sinusoids), they breach the vessel walls and spread into the surrounding tissue. Detailed microscopy work has documented how this invasion unfolds: in the early stages, leukemia cells stick to the lining of the sinusoidal walls, gaps open in that lining, and the cancer cells squeeze through. In some cases, the malignant cells simply pack the sinusoids so tightly that the vessel lining falls apart, releasing them directly into the liver tissue.²

The pattern of infiltration varies by leukemia type. Autopsy and biopsy studies show that in acute myeloid leukemia (AML), cancer cells tend to infiltrate both the portal areas and the sinusoids. In chronic myeloid leukemia, the infiltration is mainly sinusoidal. In lymphocytic leukemias, the portal tracts bear the brunt.³ These differences matter because the location of the infiltrate influences which liver functions get disrupted and what symptoms appear.

How Often the Liver Is Already Affected at Diagnosis

Many patients walk into a clinic with liver involvement before anyone even suspects leukemia. A study of pediatric patients with acute leukemia found that only about half of those with AML and roughly 45% of those with the most common childhood form (pre-B ALL) had entirely normal livers at the time of diagnosis. For T-cell ALL, the proportion with normal livers dropped to less than a quarter.⁴

Liver enlargement (hepatomegaly) was especially common in the lymphocytic leukemias, present in roughly 42% of pre-B ALL and about 59% of T-ALL patients. Actual liver dysfunction, meaning the organ was not working properly rather than simply being swollen, was most frequent in AML, affecting nearly 30% of that group.⁴ An older pediatric series found liver enlargement in more than half of children with acute leukemia at presentation.⁵ The takeaway is that liver involvement at diagnosis is common, not an outlier complication.

Recognizable Signs of Liver Involvement

The clinical picture varies widely. Some patients have no symptoms at all and the liver involvement only shows up on blood tests or imaging. Others present with unmistakable signs. The most commonly reported presentation in published case series is a cholestatic pattern, where bile flow gets blocked. This can cause yellowing of the skin and eyes (jaundice), itching, dark urine, and pale stools.⁶ In one reported AML case, imaging revealed biliary distension, gallbladder wall thickening, and hepatosplenomegaly, while a liver biopsy confirmed dense infiltration of leukemia cells in the portal areas and lobules.⁷

Not every case follows that cholestatic script, though. Some patients present with a hepatitis-like picture, where the dominant abnormality is a sharp rise in liver enzymes (transaminases) rather than bile-related markers. In at least one documented case, liver enzyme elevations persisted even after gallbladder removal but normalized once chemotherapy was started, confirming that the leukemia itself was the cause.⁶ CT imaging of leukemia patients may show organ enlargement, focal defects in the liver, or diffuse tissue infiltration.⁸

In practical terms, the signs a patient or family member might notice include:

• Abdominal fullness or pain: especially in the upper right side, caused by the liver swelling against surrounding tissues.
• Jaundice: a yellow tinge to the skin or whites of the eyes, sometimes accompanied by dark urine.
• Unexplained fatigue or confusion: if liver function deteriorates enough to impair the organ’s ability to clear toxins from the blood.
• Easy bruising or bleeding: the liver produces clotting factors, and when it fails, bruising and prolonged bleeding can worsen beyond what the leukemia itself causes.

Acute Liver Failure as the First Sign of Leukemia

In rare but devastating cases, the very first indication that anything is wrong is sudden liver failure, with the underlying leukemia only discovered afterward. A case series described three patients who presented with acute liver failure of uncertain cause; only after extensive workup was acute leukemia identified as the culprit. Despite starting cancer-directed treatment, all three died from the liver failure.⁹

A separate case report detailed a 75-year-old woman who came to the hospital with rapidly worsening fatigue, abdominal pain, and jaundice. Imaging showed a massively enlarged liver and spleen studded with nodules. Within days she developed full-blown encephalopathy (confusion from toxin buildup), skyrocketing liver enzymes, kidney failure, and severe clotting problems. She died of multiorgan failure, and autopsy confirmed extensive AML infiltration of the liver, spleen, and bone marrow.¹⁰ These cases are uncommon, but they underscore why clinicians include leukemia in the differential diagnosis for unexplained liver failure, particularly when standard causes like viral hepatitis and drug toxicity have been ruled out.

Leukostasis and Tumor Lysis Syndrome

Two emergency complications of leukemia can hammer the liver even without direct infiltration by cancer cells. Leukostasis occurs when extremely high white blood cell counts cause the blood to become thick and sluggish, clogging small vessels. The lungs and brain are the organs most often discussed in connection with leukostasis, but the liver and spleen can also suffer infarction (tissue death from blocked blood flow). One autopsy case documented severe infarctions in multiple organs, including the spleen, attributed to leukostasis in a patient with AML.¹¹

Tumor lysis syndrome (TLS) is a different mechanism entirely. When large numbers of cancer cells die rapidly, whether spontaneously or after starting treatment, they dump their contents into the bloodstream. The resulting chemical storm can overwhelm the kidneys and liver simultaneously. A case report of spontaneous TLS in a patient with lymphoma documented the full cascade: dangerously high potassium and phosphate, plummeting calcium, kidney injury, jaundice, clotting failure, and hepatic encephalopathy.¹² Although that particular case involved lymphoma, the same process can occur in aggressive leukemias with very high tumor burdens.

Chemotherapy-Related Liver Damage

Even when leukemia treatment succeeds in killing cancer cells, it can leave the liver battered. In one study of pediatric leukemia patients on maintenance chemotherapy, roughly 82% developed some degree of toxic hepatitis. About half had a moderate form, and around 8% had severe liver damage. The worst episodes clustered during the intensified “reinduction” phases of treatment.¹³

The drug 6-mercaptopurine (6-MP), a backbone of maintenance therapy for ALL, is a well-known liver offender. One pediatric trial found abnormal liver function tests in 60% of patients receiving standard treatment. When the bile-acid drug ursodeoxycholic acid (UDCA) was given alongside chemotherapy, that rate dropped to 32%, and far fewer patients needed their 6-MP dose reduced.¹⁴ This is a good example of how liver toxicity is not merely a side note: when the liver is too damaged to tolerate continued chemotherapy, treatment has to be paused or reduced, which can compromise the fight against the leukemia itself.

The encouraging side is that much of the liver injury caused by chemotherapy is reversible. A study evaluating liver function four weeks after induction chemotherapy found that markers of liver damage dropped significantly once treatment was underway and the leukemia cell burden shrank.¹⁵ So in some patients the liver injury at diagnosis comes primarily from the leukemia, and treating the cancer also treats the liver.

Liver Problems After Stem Cell Transplant

For patients who undergo a stem cell (or bone marrow) transplant as part of their leukemia treatment, an additional set of liver risks enters the picture. One of the most feared is sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD). In SOS, the small veins inside the liver become blocked, leading to painful liver swelling, fluid retention, weight gain, and jaundice. The European Society for Blood and Marrow Transplantation considers SOS a potentially life-threatening transplant complication.¹⁶ UK guidelines from the British Committee for Standards in Haematology have formalized diagnostic criteria and management strategies for this condition.¹⁷

Graft-versus-host disease (GVHD) is the other major post-transplant threat to the liver. In GVHD, the transplanted immune cells recognize the recipient’s body as foreign and attack it. When the liver is targeted, the acute form causes severe hepatitis. The chronic form leads to progressive destruction of bile ducts and, eventually, scarring (fibrosis).¹⁸ Liver dysfunction developing later after transplant can also stem from iron overload, which accumulates from repeated blood transfusions, or from reactivation of hepatitis viruses in the newly immunosuppressed patient.¹⁹ Sorting out which of these overlapping causes is responsible for abnormal liver tests in a transplant patient often requires a liver biopsy.

Fungal Infections During Treatment

Leukemia treatment hammers the immune system, and the liver can become a target for opportunistic infections, particularly fungal ones. Hepatosplenic candidiasis, where Candida fungus establishes itself in the liver and spleen, is a recognized complication. A large review found that roughly 7% of adults with acute leukemia developed hepatosplenic candidiasis, and the rate increased over the study period. Patients with acute lymphocytic leukemia were at higher risk (about 11%) than those with AML (about 5%).²⁰ Other fungi, including Mucor species, have also been identified in liver tissue of leukemia patients.²¹

These infections typically emerge as the patient’s white blood cell counts are recovering after a chemotherapy cycle. The classic presentation is persistent fever that doesn’t respond to antibiotics, with imaging showing multiple small lesions scattered through the liver and spleen. Antifungal treatment is usually prolonged, lasting months, and the infection can delay subsequent chemotherapy cycles.

How Liver Dysfunction Shapes Treatment Decisions

Liver health at diagnosis is not just a marker of disease severity; it directly influences how leukemia can be treated. A study of AML patients found that those with liver dysfunction at diagnosis were more likely to fall into higher-risk categories, had more frequent infections, and had poorer overall outcomes.²² In children with ALL, liver dysfunction during induction was associated with higher death rates during that treatment phase, and five-year survival trended lower compared with children who maintained normal liver function.²³

The practical consequence is dose adjustment. Many chemotherapy drugs used in leukemia are processed by the liver, and giving full doses to a patient whose liver is already struggling invites dangerous toxicity. Anthracyclines like daunorubicin, for example, require dose reductions based on bilirubin and transaminase levels. If bilirubin rises above a certain threshold, the drug may be cut to 75% or 50% of the standard dose, and at very high bilirubin levels the drug is withheld entirely. Cytarabine, another cornerstone drug, also needs dose cuts when liver tests are abnormal.²⁴ The balancing act is delicate: reduce the dose too much and the leukemia is undertreated; push too hard and the liver may fail.

CAR-T Therapy and the Liver

Newer treatments bring their own liver risks. Chimeric antigen receptor T-cell (CAR-T) therapy, increasingly used for certain leukemias and lymphomas, can trigger intense immune reactions that spill over into the liver. Cytokine release syndrome, the most common serious side effect of CAR-T, causes a systemic inflammatory response that frequently shows up as abnormal liver tests. A separate and more dangerous complication, called immune effector cell-associated hemophagocytic lymphohistiocytosis, can cause severe liver damage. Experts have also flagged the risk of hepatitis B virus reactivation in patients undergoing CAR-T therapy.²⁵ Because CAR-T is still relatively new, clinicians are actively refining how to tell whether abnormal liver tests after treatment reflect an expected immune reaction or a more worrisome liver injury that requires intervention.

Why Routine Liver Monitoring Matters Throughout Treatment

Given all the ways leukemia and its treatments can affect the liver, frequent monitoring of liver function is standard practice. Simple blood tests measuring liver enzymes, bilirubin, and clotting factors serve as early-warning systems. Researchers have argued that checking liver function at the time of diagnosis is itself a useful prognostic tool: patients who start out with abnormal liver tests tend to face a rougher treatment course and may need closer surveillance from the outset.²²

During chemotherapy, liver tests are checked before each cycle and sometimes more often. A rise in numbers does not necessarily mean treatment must stop. Sometimes the abnormality reflects the leukemia itself receding, and the numbers improve on their own. Other times the spike signals drug toxicity, and a dose reduction or a switch to a less hepatotoxic regimen is needed. The clinical challenge lies in distinguishing between these causes quickly enough to avoid lasting damage. For transplant patients, liver tests are monitored even more intensely, because SOS, GVHD, infection, and drug toxicity can all produce similar-looking lab abnormalities and each demands a different response.