Liver cancer

liver cancer

Epidemiology:

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a significant global health issue. It is the sixth most frequently diagnosed cancer and the fourth leading cause of cancer-related death worldwide, accounting for over 700,000 deaths annually¹.

Liver cancer often develops in people with pre-existing chronic liver diseases, especially cirrhosis. The most common underlying causes include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), excessive alcohol consumption, and non-alcoholic fatty liver disease (NAFLD), which is often linked to obesity and type 2 diabetes².

Spontaneous remission (SR) of any type of cancer is an extremely rare phenomenon and its frequency is difficult to estimate in medical practice. It has been reported that SR may account for less than 2% of all reported cases of SR of neoplasms³. Irrespective of cancer type or histopathology, SR is a very rarely reported phenomenon within the medical profession. Because cases of SR tend to be reported only when the “regression is both dramatic and durable [and] less dramatic regressions, for many reasons, tend to get overlooked and are almost never reported”⁴. It is therefore difficult to estimate the frequency with which liver cancer undergoes SR as part of its natural history. By definition, SR is the complete or partial disappearance or regression of cancer without any treatment that could be credited with its remission. Due to its rarity and the tendency for only the most "dramatic and durable" cases to be reported, the true frequency of SR in liver cancer is likely underestimated.

Clinical Characteristics:

To date, there have been 100 reported cases of SR of either primary or metastatic liver cancer. There are several clinical trends that may be observed among these cases. The patients’ age at the time of regression ranges from 14 to 92 years with a peak incidence of 60-70 years of age. Males showed much higher rates (2:1) of SR of CRC, with all cases of SR from rectal cancers occurring in males. See table 1 below for further information.

Histological and Imaging Characteristics

The predominant histological diagnosis is hepatocellular carcinoma (HCC), with tumors exhibiting varying levels of differentiation, including well-differentiated, moderately differentiated, and poorly differentiated forms. Other tumor types were not included in this analysis.

Imaging findings consistently show the presence of one or more heterogeneous masses in the liver, most commonly located in the right hepatic lobe. Common laboratory findings include elevated serum levels of the tumor markers alpha-fetoprotein (AFP) and PIVKA-II, as well as elevated liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Proposed Contributing Mechanisms

The following factors are proposed to contribute to the spontaneous regression of liver cancer, with the number of cases citing each mechanism detailed below:

• Vascular/Ischemia (36 cases): This is the most frequently proposed mechanism. It is believed that a disturbance in the tumor's blood supply, caused by factors such as portal vein thrombosis, hemorrhage-induced ischemia, or arterial embolization, leads to tumor infarction and necrosis, which results in subsequent regression.
• Immune Response (20 cases): This mechanism suggests that the patient's own immune system is responsible for the regression. Evidence for this includes histological findings of lymphocyte infiltration, macrophage overactivation, and an overall anti-tumoral immune reaction.
• Other/Systemic Factors (16 cases): Various other systemic factors are mentioned, including hormonal changes(postpartum), the use of specific herbal medicines, vitamin K administration, radiation therapy, systemic viral clearance, and hemodynamic changes associated with dialysis.
• No Reported Mechanism (30 cases): A significant portion of the cases is described as having no definitive cause for their regression, with some being explicitly labeled as "truly spontaneous" or "unspecified."

Site and extent of regressions

In the 102 cases of spontaneous regression (SR) of liver cancer, a majority of patients experienced complete regression of their tumors, with all evidence of the lesion disappearing on follow-up imaging. Several cases, however, showed a partial regression, with the tumors shrinking significantly but not fully resolving.

The site and extent of the regression varied:

• Primary Tumor Only (62 cases): The regression was confined to the primary hepatic lesion.
• Metastases Only (11 cases): The SR was observed exclusively in metastatic sites, such as lung nodules or enlarged lymph nodes, with no change to the primary liver tumor.
• Primary and Metastases (29 cases): In these cases, both the primary liver tumor and its metastases regressed simultaneously.

The follow-up period for these patients ranged from months to over a decade, with many surviving for several years after the documented SR event.

Table 1: CRC SR Cases and Clinical Characteristics

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