Pseudocirrhosis is an uncommon but clinically relevant entity that radiologically and clinically mimics liver cirrhosis in the absence of diffuse fibrosis and classic regenerative nodules^[1]. It is most frequently observed in patients with metastatic malignancies, particularly breast carcinoma, usually without known pre-existing chronic liver disease, and may evolve rapidly, leading to portal hypertension and liver failure. Historically, the term hepar lobatum carcinomatosum was introduced in 1924 to describe lobulated hepatic contours at autopsy in a woman with breast cancer^[2]. Decades later, in 1994, Young et al. proposed the term pseudocirrhosis based on clinical and radiologic features that reproduce the cirrhosis-like liver appearance in oncologic contexts^[3]. Although the exact mechanisms are not fully defined, several processes likely contribute, including sinusoidal or intra-sinusoidal neoplastic infiltration, portal venous thrombosis, perisinusoidal fibrosis, alterations of intrahepatic lymphatics, and nodular regeneration^[4]. These changes can end in clinically significant portal hypertension with ascites, varices, and splenomegaly^[5].

Pseudocirrhosis has been described primarily in metastatic breast cancer, with additional reports in pancreatic, thyroid, oesophageal, and gastroesophageal neoplasia^[6-8]. Standardized diagnostic criteria are lacking, and diagnosis is predominantly imaging-based. Early recognition and close monitoring are essential to anticipate complications of portal hypertension, including variceal bleeding and hepatic encephalopathy, which are associated with poor clinical outcomes and reduced survival^[9,10].

Unlike cirrhosis, pseudocirrhosis can progress over a short time window (approximately 1-3 months). Typical imaging findings include surface nodularity, capsular retraction, segmental volume loss, and caudate lobe hypertrophy^[11-14]. The differential diagnosis is broad and includes, among others, vascular liver disease, granulomatous liver disease and chronic drug-induced hepatotoxicity^[15].

Therefore, this narrative review aims not only to summarize the pathophysiology and imaging features of pseudocirrhosis, but also to propose a practical diagnostic framework for clinicians facing a cirrhosis-like liver morphology in oncologic patients, with particular attention to the differential diagnosis with true cirrhosis and infiltrative hepatocellular carcinoma (HCC).

The pathophysiology of pseudocirrhosis is multifactorial and not yet fully elucidated. Neoplastic cells may infiltrate the liver via arterial or portal routes, forming capillary-like networks or directly obstructing hepatic sinusoids^[16,17]. Although classically recognized in hematologic malignancies, diffuse intra-sinusoidal spread can also occur in solid tumours, particularly in poorly differentiated breast cancer^[18].

Three non-mutually exclusive mechanisms are commonly proposed: desmoplastic retraction, fibrotic scarring, and capsular retraction occurred in response to neoplastic infiltration or as a consequence of effective cytotoxic therapy around regressed metastases; nodular regenerative hyperplasia (NRH) secondary to chemotherapy-related ischemia and sinusoidal injury; sinusoidal or venular obstruction due to microscopic neoplastic infiltration or chemotherapy-related vascular injury^[14,19-22] [Figure 1].

Peritumoral desmoplastic fibrosis is considered a major driver, representing a fibrotic stromal response to tumour infiltration that leads to capsular retraction, marked lobulation, and lobar atrophy, often predominant in the right lobe^[11,23]. Hypoxia, tissue injury, and fibroblast activation, mediated by cytokines and growth factors from tumour cells or injured hepatocytes, promote collagen deposition in peritumoral regions^[24,25].

NRH represents a compensatory response to subacute or chronic vascular injury and has been associated with systemic chemotherapy, chronic immunosuppressants (including thiopurines), or antiretroviral agents^[26]. It is characterized histologically by diffuse small regenerative nodules in the absence of bridging fibrosis and can cause clinically relevant non-cirrhotic portal hypertension^[5,15,20,27]. Finally, intrahepatic venous outflow impairment may arise from external compression or intra sinusoidal obstruction by metastases, mimicking aspects of Budd-Chiari pathophysiology^[28]. For instance, in metastatic breast carcinoma, several reports have documented extensive sinusoidal dissemination of tumour cells with associated stromal desmoplasia^[29], a pattern that is typically associated with rapid clinical deterioration and poor prognosis [Table 1]. Lastly, certain chemotherapeutic agents (e.g. oxaliplatin, taxanes) directly injure sinusoidal endothelium and contribute to the morphologic and functional alterations observed in pseudocirrhosis^[19,40].

From a clinical standpoint, pseudocirrhosis should be approached as part of a stepwise differential diagnosis rather than as an isolated radiologic label. The first diagnostic question is whether the cirrhosis-like morphology reflects pre-existing or newly recognized chronic liver disease. In patients with established risk factors for HCC, infiltrative tumour must be actively excluded, particularly when alpha-fetoprotein (AFP) is markedly elevated. Conversely, pseudocirrhosis becomes more likely when a rapidly evolving nodular liver contour, capsular retraction, segmental volume loss, and portal hypertension develop in a patient with metastatic disease, especially after systemic therapy, in the absence of prior chronic liver disease and without typical HCC imaging features.

Several other clinical conditions may mimic pseudocirrhosis, both radiologically and functionally, despite having distinct aetiologies and pathophysiologic mechanisms. A proper differential diagnosis is essential to avoid misclassification and inappropriate management, particularly in oncologic patients [Figure 2 and Table 2].

HCC, the most common primary malignancy of the liver, typically arises in the context of chronic liver disease and cirrhosis. The nodular and massive growth patterns of HCC are usually radiologically remarkable and often fulfill classic imaging criteria on dynamic contrast-enhanced computed tomography or magnetic resonance imaging (MRI). Conversely, the infiltrative subtype of HCC, accounting for 7%-20% of all cases, is notoriously difficult to detect and may present as a diffuse alteration of the hepatic parenchyma without a dominant lesion^[58]. This growth pattern can involve entire lobes or even the whole liver and is often accompanied by portal vein tumour thrombosis and aggressive biological behaviour^[15,59,60].

Thus, the presence of HCC risk factors changes the diagnostic hierarchy. In a patient with chronic liver disease or cirrhosis, a new diffuse hepatic distortion should not be attributed to pseudocirrhosis until infiltrative HCC has been reasonably excluded. The diagnostic intersection between these two entities represents a critical clinical scenario where imaging features, oncologic history, and liver function all converge to guide decision-making. From a radiologic point of view, infiltrative HCC tends to show subtle or patchy arterial enhancement, often with heterogeneous washout and hypo-intensity in the hepatobiliary phase, particularly when using hepatobiliary contrast agents^[61,62]. Diffusion-weighted MRI may increase lesion detectability in these cases^[63]. In particular, hepatobiliary contrast-enhanced MRI may improve lesion conspicuity in infiltrative HCC, especially in patients with diffuse or heterogeneous parenchymal distortion. These features, however, are not pathognomonic, and similar findings can be seen in cases of pseudocirrhosis with underlying diffuse metastatic disease. Importantly, while infiltrative HCC and pseudocirrhosis may both present with nodular liver contour, capsular retraction, segmental atrophy, and signs of portal hypertension, they arise from deeply different processes^[3,14,35].

Serologic markers, especially AFP, have limited diagnostic accuracy and are no longer recommended as stand-alone tests for the diagnosis of HCC in major international guidelines. When AFP is used as a diagnostic marker, low cut-offs (e.g. 20 ng/mL) provide only moderate sensitivity but poor specificity, whereas higher thresholds of 200-400 ng/mL markedly increase specificity at the expense of very low sensitivity. In most series, AFP values ≥ 200-400 ng/mL have shown specificities close to or above 95%-99% for HCC in patients with chronic liver disease^[59,64,65]. Despite these limitations, very high AFP concentrations often carry important diagnostic information. Markedly elevated AFP values, in the hundreds or thousands of ng/mL, are strongly associated with advanced, biologically aggressive HCC and with features such as large tumour burden and portal vein invasion^[66,67]. In particular, infiltrative HCC frequently presents with elevated AFP levels, and published series report median values in the several-hundred ng/mL range, with a substantial proportion of patients exceeding conventional diagnostic thresholds^[59]. By contrast, in pseudocirrhosis related to metastatic breast cancer or other non-AFP-producing primaries, AFP levels are typically normal or only mildly elevated. Thus, while normal AFP does not exclude infiltrative HCC, a strikingly elevated AFP level in a cirrhosis-like liver should strongly favour the diagnosis of HCC over pseudocirrhosis in the appropriate clinical context^[58].

Clinicians should suspect pseudocirrhosis when a patient with metastatic cancer, particularly with liver involvement, develops a rapid change in hepatic morphology characterized by surface nodularity, capsular retraction, segmental volume loss, caudate lobe hypertrophy, and signs of portal hypertension. The suspicion is strengthened by the absence of previous chronic liver disease, a close temporal relationship with systemic therapy, and discordance between improving or stable tumour burden and worsening portal hypertensive features. Serial comparison with prior imaging is essential, because rapid evolution over weeks to a few months is one of the most useful clues distinguishing pseudocirrhosis from conventional cirrhosis.

Distinguishing between infiltrative HCC and pseudocirrhosis can be challenging; a structured diagnostic algorithm can help guide the stepwise evaluation and multidisciplinary decision-making process in this context [Figure 3].

Obviously, the key starting point is the patient’s medical history. If a patient with known metastatic disease develops a liver morphology resembling cirrhosis, especially after systemic therapy, the diagnosis of pseudocirrhosis should be favored if the radiological changes are rapid, AFP is normal or only slightly elevated, and no dominant lesions, tumor-in-vein, or typical enhancement patterns are identified. Conversely, infiltrative HCC should be strongly considered when parenchymal distortion is associated with markedly elevated or progressively rising AFP levels, hyperenhancement in the arterial phase, hypointensity in the hepatobiliary phase, diffusion restriction, tumor thrombosis of the portal vein, but especially a history of chronic liver disease.

In this context, a multimodal approach is essential. Histologic confirmation via biopsy should be considered when imaging is inconclusive, when tumour markers and imaging are discordant, when occult sinusoidal metastasis is suspected despite apparently negative imaging, or when the result would change oncologic management. Infiltrative HCC, due to its aggressive nature and poor prognosis, in addition to the frequently observed associated chronic liver disease, is typically not amenable to curative treatment. Pseudocirrhosis, although potentially associated with signs of portal hypertension and hepatic failure, does not always carry the same oncologic implications^[3,68]. In patients with ascites, portal hypertension, coagulopathy, or thrombocytopenia, the transjugular route should generally be preferred. Thus, multidisciplinary discussion involving hepatologists, oncologists, radiologists, and pathologists is recommended before discontinuing potentially effective antitumour therapy or before assigning the patient to best supportive care.

There is no disease-specific treatment for pseudocirrhosis, and management should be individualized according to the dominant mechanism, severity of portal hypertension, liver function, and oncologic status. When chemotherapy-related sinusoidal injury, NRH, or treatment-induced desmoplastic retraction is suspected, temporary interruption, dose reduction, or modification of the implicated systemic therapy should be discussed. Supportive treatment should follow the principles used for portal hypertension and be individualized according to liver function, tumour burden, and life expectancy.

In highly selected patients with symptomatic malignant pseudocirrhosis and refractory portal hypertension, transjugular intrahepatic portosystemic shunt (TIPS) has been reported as a feasible palliative option, although evidence remains limited and patient selection should be multidisciplinary^[69].

The prognosis becomes particularly poor when pseudocirrhosis is complicated by clinically significant portal hypertension. In a systematic review and meta-analysis including 389 patients^[70], portal hypertension was observed in most patients reported in case reports and case series, with ascites and oesophageal varices being the most frequent manifestations; the median time from pseudocirrhosis diagnosis to death was only 2 months in case reports and case series, whereas observational studies reported median times to death ranging from 3.6 to 8.5 months. Contemporary breast cancer cohorts confirm this adverse prognosis, with median overall survival after pseudocirrhosis diagnosis of approximately 7.6-7.9 months^[19]. The presence of clinically significant portal hypertension may further identify a subgroup with particularly poor outcomes: in one cohort, patients with endoscopically evident oesophageal or gastric varices had a median overall survival of 5 months, compared with 13 months in those without varices, and median survival after documentation of varices was only 2 months^[71]. However, these estimates should be interpreted cautiously because survival is strongly influenced by tumour subtype, tumour burden, liver function, availability of further oncologic therapy, and heterogeneous definitions of portal hypertension across studies.

Although pseudocirrhosis is often associated with poor prognosis, partial or complete regression has been reported in selected cases, especially when the process is driven by treatment-related injury or scarring around regressed metastases rather than uncontrolled diffuse tumour infiltration^[6]. Therefore, early recognition is clinically relevant because timely adjustment of systemic therapy and management of portal hypertension may preserve liver function and allow continuation or resumption of oncologic treatment.

Pseudocirrhosis is often a rapidly progressive condition with a poor prognosis, reflecting both the underlying malignancy and treatment-related liver injury. Early recognition allows for closer monitoring of hepatic function, timely adjustment or withdrawal of potentially hepatotoxic systemic therapies, and earlier institution of supportive measures before overt hepatic failure precludes further oncologic options. Supportive care includes management of ascites, endoscopic treatment of varices, and management of hepatic encephalopathy, while in severe cases advanced interventions such as TIPS may be considered for refractory portal hypertension. In selected patients, partial regression of the pseudo-cirrhotic morphology after modification or discontinuation of systemic therapy has been reported, but this appears to be the exception rather than the rule.

At the same time, in patients with a cirrhosis-like liver and equivocal imaging findings, early histologic confirmation plays a pivotal role. Indeed, only a definite diagnosis reached by liver histology can safely justify active tumour-directed treatment, including rescue chemotherapy regimens, before progressive liver failure irreversibly limits these options.

Finally, current evidence on pseudocirrhosis remains weak and largely based on case reports, small retrospective cohorts, and heterogeneous systematic reviews. Diagnostic definitions vary across studies, histologic confirmation is available only in a minority of cases, and the relative contribution of different pathophysiological mechanisms is often difficult to identify. These limitations currently prevent the development of validated diagnostic criteria or evidence-based management algorithms. Future studies should aim to establish prospective multicentre registries with standardized imaging criteria, systematic comparison with previous imaging, predefined definitions of portal hypertension, integrated radiology-pathology correlation whenever biopsy is feasible and particular attention to modern systemic therapies.