Liver cancer

Alqutub, 2011⁵

65-year old male; 1-week history of abdominal pain; anorexia and 12-lb weight loss over two months prior; history of hypertension, diabetes, hypercholesterolemia and obesity; blood pressure 120/60

right hepatic lobe

over period of a few months, symptoms improved and tumour showed radiological evidence of spontaneous involution coupled with decrees in AFP levels, meeting criteria for spontaneous resolution; follow-up CT 14 weeks after initial diagnosis showed significant interval reduction in size of mass with associated atrophy of right hepatic lobe; occlusion of right portal veing at 14 weeks was still present, but main portal vein thrombus and periaortic lymphadenopathy had resolved; CT scan 28 weeks after initial diagnosis showed persistent right portal vein occlusion and small hypodensity in posterior segment of right hepatic lobe; CT scan 14 months from initial diagnosis showed small irregular hypodensity in posterior segment of right hepatic lobe with no area of abnormality anywhere else; ultrasound 2 years after initial diagnosis showed no liver lesions and AFP level remained below 10 ug/L

speculation that local ischemia due to rapid tumour growth resulted in intra tumoural bleeding and/or hemorrhagic necrosis (based on cases in literature)

over period of a few months, symptoms improved and tumour showed radiological evidence of spontaneous involution coupled with decrees in AFP levels, meeting criteria for spontaneous resolution; follow-up CT 14 weeks after initial diagnosis showed significant interval reduction in size of mass with associated atrophy of right hepatic lobe; occlusion of right portal veing at 14 weeks was still present, but main portal vein thrombus and periaortic lymphadenopathy had resolved; CT scan 28 weeks after initial diagnosis showed persistent right portal vein occlusion and small hypodensity in posterior segment of right hepatic lobe; CT scan 14 months from initial diagnosis showed small irregular hypodensity in posterior segment of right hepatic lobe with no area of abnormality anywhere else; ultrasound 2 years after initial diagnosis showed no liver lesions and AFP level remained below 10 ug/L

Arora & Madhusudhana et al., 2011⁶

54-year old African-American male; chronic hepatitis C infection; medical history included coronary artery disease, hypertension, dyslipidemia, peripheral neuropathy, chronic lumbago; meds include metoprolol, albuterol inhaler, oxycodone, hydrochlorothiazide, nitroglycerine, aspirin, gabapentin, doxazosin, ezetimibe, cyclobenzaprine

right hepatic lobe

admitted for pneumonia 22 months after 2- months follow up at which time it was discovered that HCC was in remission; continues to be in remission 4 years after initial diagnosis

None reported

admitted for pneumonia 22 months after 2- months follow up at which time it was discovered that HCC was in remission; continues to be in remission 4 years after initial diagnosis

Bastawrous et al., 2012⁷

63-year old Caucasian man with hepatitis C and Child's class A cirrhosis presented with mental status changes related to hepatic encephalopathy, demonstrated asterixis and presence of ascites; reported recent fatigue and anorexia; medical history included post-traumatic stress disorder and thrombocytopenia

right hepatic lobe

CT two months after diagnosis showed that known mass had decreased in size and was now predominately cystic; multiphase CT showed that tumour was no uniformly hypodense and cystic on all four phases, without arterial enhancement or portal venous phase washout, no new masses detected; CT 10 months after initial presentation showed continued reduction in size, was non-enhancing and remained cystic with no additional masses

proposed vascular etiology related to hemorrhage-induced ischaemia, possible that acute onset of haemodynamic instability had altered the tumoural blood supply, resulting in tumour infarction and necrosis

CT two months after diagnosis showed that known mass had decreased in size and was now predominately cystic; multiphase CT showed that tumour was no uniformly hypodense and cystic on all four phases, without arterial enhancement or portal venous phase washout, no new masses detected; CT 10 months after initial presentation showed continued reduction in size, was non-enhancing and remained cystic with no additional masses

Bhardwaj et al., 2014⁸

74-year old woman presented with back pain and blood in urine; history of alcohol misuse, hypertension, cholecystectomy and tubal ligation

inferior left hepatic lobe

2 months later a CT scan showed a dramatic reduction in number and size of lesions and liver tests had returned to normal; subsequent CT scans over the next 19 months continued to show regression or resolution of all lesions

no specific mechanism for this case offered

2 months later a CT scan showed a dramatic reduction in number and size of lesions and liver tests had returned to normal; subsequent CT scans over the next 19 months continued to show regression or resolution of all lesions

Jang et al., 2000⁹

54-year old female; past medical history includes liver cirrhosis associated with hepatitis B virus

right hepatic lobe

refused any therapy, was admitted 4 years after initial diagnosis for nausea, vomiting and diffuse abdominal pain; physical exam, lab findings, ultrasound and CT showed no evidence of lesion, just vague wedge-shaped area with low density in hepatic dome

cirrhotic changes observed on imaging study could have caused ischemia, contributing to spontaneous regression of tumour

refused any therapy, was admitted 4 years after initial diagnosis for nausea, vomiting and diffuse abdominal pain; physical exam, lab findings, ultrasound and CT showed no evidence of lesion, just vague wedge-shaped area with low density in hepatic dome

Kim, 2015¹⁰

57-year old male with HBV-related cirrhosis; diagnosed as HBeAg-positive CHB and on entecavir therapy

segment 6 of liver

within 5 weeks after diagnosis, AFP level declined to 50 ng/mL prior to surgery, surgical specimen showed complete necrosis of tumour rimmed by inflamed fibrous capsule, background of mass showed HBV-related mixed micro and macronodular cirrhosis with infiltration of lymphoplasma cells and focal granulomatous inflammation

host immune response based on lymphoplasma cell infiltration with granulomatous inflammation

within 5 weeks after diagnosis, AFP level declined to 50 ng/mL prior to surgery, surgical specimen showed complete necrosis of tumour rimmed by inflamed fibrous capsule, background of mass showed HBV-related mixed micro and macronodular cirrhosis with infiltration of lymphoplasma cells and focal granulomatous inflammation

Lim et al., 2014¹¹

64-year-old male, previously undergone right lobectomy of liver due to HCC in October 2006, chronic hepatitis B virus carrier

liver + lung & adrenal mets

patient returned for follow-up in May 2009, no change; in September 2009, symptoms had improved and chest regiograph showed that all metastatic nodules had disappeared and serium AFP levels had decreased, regression of HCC tumour observed; CT scan in December 2009 showed that all metastatic nodules in lung and lesions in adrenal glands and lymph nodes had disappeared; follow-up CT scans showed no recurrent lesions and chest radiograph showed no metastatic lesions, serum AFP and PIVKA II levels within normal; patient is alive with no symptoms as of May 2013

None reported

patient returned for follow-up in May 2009, no change; in September 2009, symptoms had improved and chest regiograph showed that all metastatic nodules had disappeared and serium AFP levels had decreased, regression of HCC tumour observed; CT scan in December 2009 showed that all metastatic nodules in lung and lesions in adrenal glands and lymph nodes had disappeared; follow-up CT scans showed no recurrent lesions and chest radiograph showed no metastatic lesions, serum AFP and PIVKA II levels within normal; patient is alive with no symptoms as of May 2013

Matsuoka et al., 2015¹²

67-year-old man, obese, the patient had begun a diet three years earlier and had succeeded in reducing his weight by approximately 5 kg. Past medical history of hypertension at 48 years of age and diabetes mellitus and hepatic dysfunction due to hepatic steatosis at 55 years of age, with no history of transfusion. He had no history of alcohol consumption or smoking and no family history of note.

liver

The patient’s postoperative course was favorable, and he was discharged from the hospital 11 days after undergoing surgery. He has since visited the hospital regularly for over three years, with no signs of recurrence.

spontaneous regression due to the presence of both arterial and portal vein thrombi.

The patient’s postoperative course was favorable, and he was discharged from the hospital 11 days after undergoing surgery. He has since visited the hospital regularly for over three years, with no signs of recurrence.

Meza-Junco et al., 2007¹³

56-year-old woman with liver cirrhosis due to HCV infection

Liver

Six months later, the tumour had been diminished, its dimensions were 3x2.5 cm. In August of the same year, the tumour was surgically removed with the segments V and VIII of the liver. The pathology report was of a hepatocellular carcinoma moderately differentiated of 2.8 vs 2.6 cm, margins were clear of tumour, there was imporightant necrosis around the tumour, and it also has macronodular cirrhosis with intense activity (Figure 3). The patient did not receive adjuvant treatment, and after 25 months of surgery she is doing well, with no evidence of tumour recurrence at CT scan and the AFP level is still within the normal range.

disturbance of the blood supply on the peripheral side

Six months later, the tumour had been diminished, its dimensions were 3x2.5 cm. In August of the same year, the tumour was surgically removed with the segments V and VIII of the liver. The pathology report was of a hepatocellular carcinoma moderately differentiated of 2.8 vs 2.6 cm, margins were clear of tumour, there was imporightant necrosis around the tumour, and it also has macronodular cirrhosis with intense activity (Figure 3). The patient did not receive adjuvant treatment, and after 25 months of surgery she is doing well, with no evidence of tumour recurrence at CT scan and the AFP level is still within the normal range.

Nakajima, 2004¹⁴

80-year-old man, He drank 350 mL of beer every day but had no history of the use of herbal medicines

liver

Because the patient wanted to undergo an operation for gallbladder stones, preoperative evaluation for cholecystectomy was carried out. In December 2000, just before the operation, a CT scan showed that Lipiodol was accumulated in the tumour in S4 and that the cystic mass in S6 was decreased in size spontaneously, down to 57 mm×44 mm. Celiac ARTeriogram one year later from the first visit, showed that the previous tumour stain in S4 disappeared. The super mesenteric ARTeriogram demonstrated 2 tumour stains; one was in S6, which was previously hypovascular, and the other was in S8. Transarterial embolization with gel foam was repeated but the tumour resisted therapy, with rapid invasion and intrahepatic metastasis

local ischemia, leading to intratumoural bleeding or hemorrhagic necrosis

Because the patient wanted to undergo an operation for gallbladder stones, preoperative evaluation for cholecystectomy was carried out. In December 2000, just before the operation, a CT scan showed that Lipiodol was accumulated in the tumour in S4 and that the cystic mass in S6 was decreased in size spontaneously, down to 57 mm×44 mm. Celiac ARTeriogram one year later from the first visit, showed that the previous tumour stain in S4 disappeared. The super mesenteric ARTeriogram demonstrated 2 tumour stains; one was in S6, which was previously hypovascular, and the other was in S8. Transarterial embolization with gel foam was repeated but the tumour resisted therapy, with rapid invasion and intrahepatic metastasis

Noij et al., 2017¹⁵

74-year old Caucasian male, non-smoker and consumed 2 units of alcohol daily.

liver

After six months from diagnosis, the patient attended for reevaluation of his disease. Over that time he had suffered a cerebrovascular accident (CVA) with ensuing partial hemiparesis. CT scan revealed that the pulmonary lesion had disappeared, whereas the suspicious hepatic lesion and the lesion anterior to the pericardium had significantly decreased in size.

None reported

After six months from diagnosis, the patient attended for reevaluation of his disease. Over that time he had suffered a cerebrovascular accident (CVA) with ensuing partial hemiparesis. CT scan revealed that the pulmonary lesion had disappeared, whereas the suspicious hepatic lesion and the lesion anterior to the pericardium had significantly decreased in size.

Nouso et al., 2005¹⁶

85-year-old man with liver cirrhosis due to HCV and diabetes mellitus. no history of alcohol drinking or blood transfusion. He did not smoke and was not taking any medicine, but was under intermediate-acting insulin (12 U/d) injection. He had undergone surgery for prostate hypertrophy 3 years before the present admission.

liver

CE-CT, 5 months after starting vitamin K, demonstrated that the tumour sizes were remarkably decreased and the diameter of the main tumour was 5.5 cm. US demonstrated that the tumour regressed and the margin of the tumour became obscure

blood shortage induced by rapid tumour growth or regression due to vitamin K administration

CE-CT, 5 months after starting vitamin K, demonstrated that the tumour sizes were remarkably decreased and the diameter of the main tumour was 5.5 cm. US demonstrated that the tumour regressed and the margin of the tumour became obscure

Ohtani, 2015¹⁷

69-year-old man with chronic hepatitis C, diagnosed in 2001 and a gastric ulcer. He had no known history of a blood transfusion or medication such as anticoagulant drugs and vitamin K. He was, however, a heavy drinker.

liver

2 months after the first US, and a new US showed a 5.1 ¥ 5.0-cm liver tumour in S4. The tumour showed a mosaic pattern with a halo. 9 months after, Dynamic CT was performed revealed the previous tumour in S4 to have decreased to 2.0cm in diameter, but it was not enhanced

possibly related to a disturbance of the blood supply on the peripheral side, such as the formation of a thick capsule

2 months after the first US, and a new US showed a 5.1 ¥ 5.0-cm liver tumour in S4. The tumour showed a mosaic pattern with a halo. 9 months after, Dynamic CT was performed revealed the previous tumour in S4 to have decreased to 2.0cm in diameter, but it was not enhanced

Okano & Ohana et al., 2015¹⁸

A 73-year-old man with hepatitis B virus (HBV) infection. He consumed 25 g of alcohol daily for 50 years and had also smoked 10 cigarettes per day for 50 years.

liver

Anterior lobectomy of the liver was planned. However, 1 month after the initial diagnosis, a plain MRI disclosed a regression of the tumour to 6 mm, and the AFP serum level decreased to 87.8 ng/ml. He had stopped alcohol consumption and smoking after the HCC diagnosis. Six months after the initial diagnosis, follow-up MRI showed no mass

ischemia secondary to angiography

Anterior lobectomy of the liver was planned. However, 1 month after the initial diagnosis, a plain MRI disclosed a regression of the tumour to 6 mm, and the AFP serum level decreased to 87.8 ng/ml. He had stopped alcohol consumption and smoking after the HCC diagnosis. Six months after the initial diagnosis, follow-up MRI showed no mass

Okano, 2013¹⁹

77-year-old man with alcoholic liver cirrhosis, Child-Pugh class B. No history of hypertension, diabetes mellitus, and atherosclerosis. He had been a regular drinker, consuming approximately 120 g/day of alcohol every day for 50 years. He had smoked 20 cigarettes per day for 50 years.

liver

One months after the diagnosis, tumour markers decreased, the mass in S8 decreased to 30 mm and became completely necrotic on CT ARTeriography. The 15-mm mass in the S8-7 diminished to 10 mm and was described as an enhanced lesion

disrupatiention of the feeding artery associated with angiography or arterial thrombosis

One months after the diagnosis, tumour markers decreased, the mass in S8 decreased to 30 mm and became completely necrotic on CT ARTeriography. The 15-mm mass in the S8-7 diminished to 10 mm and was described as an enhanced lesion

Saito, 2014²⁰

75-year-old man with chronic hepatitis C and diabetes mellitus. no history of alcohol abuse, smoking, blood transfusion, or steroid intake. He took ursodeoxycholic acid for a liver function disorder pointed out 20 years ago.

liver with lung mets

At 3 months after the initial medical examination, the serum tumour markers had decreased markedly. After 9 months, ab- dominal CT revealed that the liver mass had markedly decreased in size and the multiple nodules in the bilateral lungs had disappeared. After 13 months, HCC of 5 cm in size was detected in segment 5/6 of the liver. At 15 months after the first visit, because there was no further decrease in tumour size in the imaging studies and an increase in tumour markers, TACE was done with a second one 13 months after.

None reported

At 3 months after the initial medical examination, the serum tumour markers had decreased markedly. After 9 months, ab- dominal CT revealed that the liver mass had markedly decreased in size and the multiple nodules in the bilateral lungs had disappeared. After 13 months, HCC of 5 cm in size was detected in segment 5/6 of the liver. At 15 months after the first visit, because there was no further decrease in tumour size in the imaging studies and an increase in tumour markers, TACE was done with a second one 13 months after.

Tocci, 1990²¹

79 year old man, active liver cirrhosis (non-HAV, non-HNV), he used prednisone + azathiopine for 3 months. All treatment was stopped in march.

liver

5 months later a US should tumour size reduciton. A CT/US control after 1 month showed further reduction. 3 years later the tumour disappeared.

Severe hemorrhagic shock related

5 months later a US should tumour size reduciton. A CT/US control after 1 month showed further reduction. 3 years later the tumour disappeared.

Uenishi, 2000²²

65-year-old Japanese man, no notable family history. Hisotry of DM and chronic hepatitis secondary to daily alcohol usage for 40 year.

liver

A 1 year later follow up CT showed the hepatic mass to have deceased to 7cm in diameter. An arterial porightogram demonstrated a complete obstruction of the right posterior branch of the portal vein. Biopsy of the especimen retrieved from the lobectomy, demonstrated a necrotic core of the mass with a thick capsule.

Disturbance in both the portal venous and hepatic artery flow

A 1 year later follow up CT showed the hepatic mass to have deceased to 7cm in diameter. An arterial porightogram demonstrated a complete obstruction of the right posterior branch of the portal vein. Biopsy of the especimen retrieved from the lobectomy, demonstrated a necrotic core of the mass with a thick capsule.

Wang, 2015²³

50-year-old man there was no previous history of heavy alcohol intake, operations, or blood transfusions.

liver

no info

overactivation of CD163+ macrophages

no info

Yang, 2015²⁴

56-year-old man, 15-year history of chronic liver disease related to HBV

liver

one months after the second hospital discharge, no masses were found on abdominal US

both the spontaneous HBsAg seroconversion and the HCC regression could be trig- gered by restoration or reinforcement of virus-specific T-cell immunity

one months after the second hospital discharge, no masses were found on abdominal US

Yano, 2005²⁵

71-year-old woman with history of chronic HCV for ten years. No history of alcohol abuse, smoking, blood transfusion, or steroid intake.

liver

Histological findingsdemonstrate capsular damage or rupture associated with arterial injury prior to surgery.

Local hepatic factor

Histological findingsdemonstrate capsular damage or rupture associated with arterial injury prior to surgery.

Feo, 2014²⁶

71-year-old woman, HCV chronic infection of 8 years without any special treatment. no past medical and family history of note and did not smoke or drink

liver

Three months later, a repeat abdominal ultrasound demonstrated a shrinkage of the hepatic lesion and thrombosis of the feeding artery. CT scan showed only vague signs of a hepatic tumour, and the serum AFP level was in the normal range

Tumour infarction secondary to vascular occlusion

Three months later, a repeat abdominal ultrasound demonstrated a shrinkage of the hepatic lesion and thrombosis of the feeding artery. CT scan showed only vague signs of a hepatic tumour, and the serum AFP level was in the normal range

Sasaki, 2013²⁷

79-year-old male patient, hypertension and chronic heart failure. He had a history of alcohol abuse. Child-Pugh A

liver

Preoperative MRI revealed a faint high-intensity tumor in T1WI, similar to the results 2 months prior. However, T2WI and DWI showed a lesion with higher intensity than that seen 2 months prior . These findings were suggestive of HCC with spontaneous regression.

no info

Preoperative MRI revealed a faint high-intensity tumor in T1WI, similar to the results 2 months prior. However, T2WI and DWI showed a lesion with higher intensity than that seen 2 months prior . These findings were suggestive of HCC with spontaneous regression.

Alam, 2004²⁸

61-year-old male, full-time engineer, type 2 diabetes mellitus and hypertension, and was also being worked up for aortic valve replacement for severe aortic stenosis, he was on metformin, acute myeloid leukemiaodipine, aspirin, ramipril, insulin, and simvastatin

liver

Follow-up CT five months later showed continued regression of tumour and lymphadenopathy; however, the AFP level was margin- ally higher at 19

tumour tissue-specific immune-mediated mechanism

Follow-up CT five months later showed continued regression of tumour and lymphadenopathy; however, the AFP level was margin- ally higher at 19

Blondon, 2004²⁹

Case 1: 64-year-old man. Past history of heavy drinking.

liver

Three months later, clinical condition improved and AFP returned to normal values. CT showed regression of all liver tumours, with a centimetric cyst appearance of all except one. Histological study of the specimen (obtained from surgery) confirmed a well-differentiated encapsulated HCC with the presence of marked inflammation, necrosis with calcifications, and fibrosis.

immune activation inducing specific anti-tumoural reaction by T-cell cytotoxicity.

Three months later, clinical condition improved and AFP returned to normal values. CT showed regression of all liver tumours, with a centimetric cyst appearance of all except one. Histological study of the specimen (obtained from surgery) confirmed a well-differentiated encapsulated HCC with the presence of marked inflammation, necrosis with calcifications, and fibrosis.

Blondon, 2004²⁹

case 2: 70-year-old woman, history of alcoholism

liver

Ultrasonography 10 months after the diagnosis showed diffuse liver heterogeneity, and 5 months later only one remaining 47 mm tumour in the posterior inferior segment. At that time serum alpha-fetoprotein was decreased. She was admitted to hospital 18 months after the initial diagnosis for massive digestive bleeding related to rupture of oesophageal varices. CT showed ascitis, regression of all liver tumours, with a cystic appearance of al

Ultrasonography 10 months after the diagnosis showed diffuse liver heterogeneity, and 5 months later only one remaining 47 mm tumour in the posterior inferior segment. At that time serum alpha-fetoprotein was decreased. She was admitted to hospital 18 months after the initial diagnosis for massive digestive bleeding related to rupture of oesophageal varices. CT showed ascitis, regression of all liver tumours, with a cystic appearance of al

Cheng, 2004³⁰

74-year-old male, history of well-controlled type 2 diabetes mellitus and hypertension. There was no evidence of hepatitis, liver cirrhosis, or hepatocellular cancer in his family members

liver

Six months after taking the decoction; the tumor shrank from 10 cm to about 4 cm in diameter. 3 months later CT showed nearly complete shrinkage of the tumor in the left hepatic lobe; only a small residual tumor remained at the top of the left lobe. AFP returned within normal range

Six months after taking the decoction; the tumor shrank from 10 cm to about 4 cm in diameter. 3 months later CT showed nearly complete shrinkage of the tumor in the left hepatic lobe; only a small residual tumor remained at the top of the left lobe. AFP returned within normal range

Chiesara, 2014³¹

65-year-old Caucasian man with a his- tory of non-alcoholic steatohepatitis.

liver

After six months a CT scan showed a marked reduction in size of the major lesion from 9.5 cm to 3.3 cm and a substantial reduc- tion of the number of the other smaller lesions. Six months later fur- ther improvement of the radiological findings was observed: the main nodular lesion was 2.5cm and only three satellite lesions unchanged in size were observed One year later the patient was symptom- free and a CT scan showed the main lesion reduced to 2.2 cm and only one satellite nodule.

possible mechanisms include the use of herbal medicine (AA), ischaemic and inflammatory processes

After six months a CT scan showed a marked reduction in size of the major lesion from 9.5 cm to 3.3 cm and a substantial reduc- tion of the number of the other smaller lesions. Six months later fur- ther improvement of the radiological findings was observed: the main nodular lesion was 2.5cm and only three satellite lesions unchanged in size were observed One year later the patient was symptom- free and a CT scan showed the main lesion reduced to 2.2 cm and only one satellite nodule.

Clos, 2017³²

72-year-old male, who consumed more than 80 g of alcohol per day, history of hypertension, under pharmacological treatment, and chronic alcoholic liver disease

liver

3 months later, MRI was repeated for restating showing a decrease in the size of the nodule (14 × 16 mm), which was well-defined and hypointense in T1, and heterogeneous with poor peripheral contrast uptake in the late venous phase. An additional histological study was also performed, showing necrotic tissue and abundant macrophages. The histological study conducted on the surgical specimen showed a hyalinised nodular lesion mea- suring 16 × 20 × 8 mm, with no signs of malignancy

3 months later, MRI was repeated for restating showing a decrease in the size of the nodule (14 × 16 mm), which was well-defined and hypointense in T1, and heterogeneous with poor peripheral contrast uptake in the late venous phase. An additional histological study was also performed, showing necrotic tissue and abundant macrophages. The histological study conducted on the surgical specimen showed a hyalinised nodular lesion mea- suring 16 × 20 × 8 mm, with no signs of malignancy

Del & Oggio et al., 2009³³

77-year-old woman, hepatitis C was diagnosed at the age of 69, cholecystectomy for gallstones at the age of 30, partial thyroidectomy for multinodular goiter at the age of 35 and hysterectomy for uterine le-year-old maleioma at the age of 47

Liver

she was waiting for a partial right liver resection and 3 months after the onset of symptoms, the pain gradually abated and the analgesics could be discontinued. A control CT scan showed a reduction in size of the focal liver lesion to 2.8 cm. Laboratory tests showed normalization of AFP levels. Another CT scan demonstrated a further reduction in size of the focal lesion whose diameter was now 1.8 cm.

strong immunologic reaction against tumour antigens.

she was waiting for a partial right liver resection and 3 months after the onset of symptoms, the pain gradually abated and the analgesics could be discontinued. A control CT scan showed a reduction in size of the focal liver lesion to 2.8 cm. Laboratory tests showed normalization of AFP levels. Another CT scan demonstrated a further reduction in size of the focal lesion whose diameter was now 1.8 cm.

Gomez & Anz et al., 1998³⁴

66-year-old man, chronic hepatitis C virus and chronic gastritis, no history of alcohol consumption or blood transfusions

Liver with multiple metastases

the patient began to improve clinically and recover his appetite. The sternoclavicular lesions gradually disappeared and the abdominal pain remitted. Disappearance of the intraabdominal (confirmed by CT) and cutaneous masses in the sternoclavicular region 16 months after resection of the HCC

possible immune mechanism

the patient began to improve clinically and recover his appetite. The sternoclavicular lesions gradually disappeared and the abdominal pain remitted. Disappearance of the intraabdominal (confirmed by CT) and cutaneous masses in the sternoclavicular region 16 months after resection of the HCC

Grossmann, 1995³⁵

A 52-years-old man

Liver

At repeat laparotomy 14 months after initial diagnosis, intraoperative ultrasound failed to disclose a hepatic mass, and multiple biopsies stowed no evidence of malignancy.

At repeat laparotomy 14 months after initial diagnosis, intraoperative ultrasound failed to disclose a hepatic mass, and multiple biopsies stowed no evidence of malignancy.

Harimoto, 2012³⁶

73-year-old man, dialysis three times a week due to diabetic renal failure.

liver with lung mets

Five months after hepatectomy, the multiple lung metastases had completely regressed and the AFP and PIVKAII levels were both normalized

Extended posterior segmentectomy

Five months after hepatectomy, the multiple lung metastases had completely regressed and the AFP and PIVKAII levels were both normalized

Ikuta, 2002³⁷

60-year-old man

colon + liver mets

Nine months after surgery, the patient stated that he was feeling well, and reported a weight gain of 5 kg. The CT of the abdomen showed a remarkable regression of liver tumors in both lobes

extensive tumor necrosis

Nine months after surgery, the patient stated that he was feeling well, and reported a weight gain of 5 kg. The CT of the abdomen showed a remarkable regression of liver tumors in both lobes

Kaczynski, 1998³⁸

73-year-old man, use of digitalis for treatment of transient dysrhythmia.

Liver

coeliac angiography was performed 15 months later; no tumour was seen.

coeliac angiography was performed 15 months later; no tumour was seen.

Kato, 2004³⁹

77-year-old male, type 2 diabetes mellitus, He had smoked 20 cigarettes per day since adolescence

Liver + lungs mets

Four months after the diagnosis, Radiological studies revealed a wedge-shaped low-density area (indicating necrosis of HCC) in the liver and the disappearance of multiple nodular lesions in both lungs. Tumor markers returned to normal values

Four months after the diagnosis, Radiological studies revealed a wedge-shaped low-density area (indicating necrosis of HCC) in the liver and the disappearance of multiple nodular lesions in both lungs. Tumor markers returned to normal values

Kato, 2004³⁹

72-year-old male, He had smoked 10 cigarettes per day for 50 years.

liver

2 years later, a CT revealed a small ellipatientic cystic region in the anterior segment and a reduced size of heterogeneous low-density area with enhanced circumference in the posterior segment of the liver. PIVKA-II had markedly decreased to the normal range but AFP was double the original value

2 years later, a CT revealed a small ellipatientic cystic region in the anterior segment and a reduced size of heterogeneous low-density area with enhanced circumference in the posterior segment of the liver. PIVKA-II had markedly decreased to the normal range but AFP was double the original value

Kojima, 2006⁴⁰

A 79-year-old man, chronic hepatitis C and liver cirrhosis

Liver + lungs mets

Six months later, ab- dominal dynamic enhanced MRI indicated disappear- ance of the tumor in the S8 region and plain chest CT showed that the nodular lesions had disappeared. AFP and PIVKA-II levels had decreased to normal values, as of 6 months later, as the primary lesion and lung metastases regressed.

Regression could have been attributable to the antitumor effects of P. linteus.

Six months later, ab- dominal dynamic enhanced MRI indicated disappear- ance of the tumor in the S8 region and plain chest CT showed that the nodular lesions had disappeared. AFP and PIVKA-II levels had decreased to normal values, as of 6 months later, as the primary lesion and lung metastases regressed.

Komatsu, 2012⁴¹

65-year-old man, one episode of duodenal bulb ulcer 35 years earlier

Liver

6 months later, early-phase contrast-enhanced CT showed a high-density tumor in S7, The diameter of the tumor was 3–4 cm and the tumor volume had decreased remarkably compared to the previous CT. 2 years after diagnosis, serum concentration of PIVKA-II had decreased dramatically. In addition, a CT scan confirmed that the tumor had completely disappeared

6 months later, early-phase contrast-enhanced CT showed a high-density tumor in S7, The diameter of the tumor was 3–4 cm and the tumor volume had decreased remarkably compared to the previous CT. 2 years after diagnosis, serum concentration of PIVKA-II had decreased dramatically. In addition, a CT scan confirmed that the tumor had completely disappeared

Kondo, 2006⁴²

70-year-old man, history of heavy alcohol intake, liver cirrhosis with esophageal varices

Liver

One more later, CT showed viable tumor volume shrinkage, and the AFP level decreased

One more later, CT showed viable tumor volume shrinkage, and the AFP level decreased

Kondo, 2006⁴²

75-year-old man, postive HCV

liver with lung mets

4 months after TAE, follow-up CT and AFP did not show any relapse of HC. 4 months after discontinueatin chemotherapy, the multiple lung nodules had clearly decreased in number and in size

4 months after TAE, follow-up CT and AFP did not show any relapse of HC. 4 months after discontinueatin chemotherapy, the multiple lung nodules had clearly decreased in number and in size

Kondo, 2006⁴²

67-year-old man, multiple liver tumors, social drinker

liver

1 year after relapse, AFP levels decreased, CT showed shrinkage of the primary liver mass and the disappearance of the pleural effusion and ascites

1 year after relapse, AFP levels decreased, CT showed shrinkage of the primary liver mass and the disappearance of the pleural effusion and ascites

Kondo, 2006⁴²

67-year-old man, HCC diagnosis

liver with lung mets

Six months after CAMs his performance status had improved and the AFP level had decreased. The multiple lung nodules and liver tumors had clearly disappeared.

Six months after CAMs his performance status had improved and the AFP level had decreased. The multiple lung nodules and liver tumors had clearly disappeared.

Lee, 2000⁴³

44-year-old male, heavy drinker for the past 5 years

Liver + lungs mets

5 months later the patient felt better than before, the AFP level decreased, CT showed a small tumour

intratumoral event

5 months later the patient felt better than before, the AFP level decreased, CT showed a small tumour

Lee, 2000⁴³

63 year-old man, HBV infection for the past 15 years

liver

Three months later the liver was not palpable and AFP return to normal values. One year later a CT showed that the previous tumour had schrunk to 5cm. 1 year later, US demonstrated that the previous compression of the IVC by the original tumour had disappeared. 3 years later, the original tumour had become smaller.

intratumoral event

Three months later the liver was not palpable and AFP return to normal values. One year later a CT showed that the previous tumour had schrunk to 5cm. 1 year later, US demonstrated that the previous compression of the IVC by the original tumour had disappeared. 3 years later, the original tumour had become smaller.

Li, 2003⁴⁴

53-year-old man, history of HBV

liver

Microscopic examination showed no malignant cells

inflammatory reaction

Microscopic examination showed no malignant cells

Luciani, 2001⁴⁵

77-year-old with 10 year history of HBV infection and liver cirrhosis

liver

A second abdominal CT scan was thus performed 7 months later no hypervascular nodule could be detected. A 5-mm non-enhancing lesion was present at the location of the initial nodule. After 30- months follow-up the patient is well and recent US examinations have been unable to detect initial liver lesion recurrence.

tumor necrosis

A second abdominal CT scan was thus performed 7 months later no hypervascular nodule could be detected. A 5-mm non-enhancing lesion was present at the location of the initial nodule. After 30- months follow-up the patient is well and recent US examinations have been unable to detect initial liver lesion recurrence.

Misawa, 1999⁴⁶

62-year-old man, history of chronic HBV with liver cirrhosis for 10 years. Stroke

liver

2 years after admission, AFP normalized and the size of the tumor had reduced to 1.5 cm, by the end of that year it went almost undetectable.

Hypoxic condition that leads to tumor necrosis

2 years after admission, AFP normalized and the size of the tumor had reduced to 1.5 cm, by the end of that year it went almost undetectable.

Nakai, 2001⁴⁷

76-year-old man with liver cirrhosis caused by the hepatitis C virus

liver

On abdominal CT in October 1998, no tumors were noted, except for a small lesion that was probably a scar, and the PIVKA-II level was normalized

immunological mechanism.

On abdominal CT in October 1998, no tumors were noted, except for a small lesion that was probably a scar, and the PIVKA-II level was normalized

Nakayama, 2012⁴⁸

92-year-old Japanese woman with cryptogenic chronic liver disease for about 10 years. Schistosoma japonica infection

liver

On follow up in July 2011, a sudden return of AFP to normal values. A dynamic CT in August 2011 showed complete disappearance of HCC and marked fatty change of the liver

immune response

On follow up in July 2011, a sudden return of AFP to normal values. A dynamic CT in August 2011 showed complete disappearance of HCC and marked fatty change of the liver

Nam, 2005⁴⁹

65-year-old Korean man, 100 g of alcohol per day for 30 years

liver + skull mets

Ten months after radiation therapy, the follow-up CT revealed a marked reduction in the size of the hepatic mass and a reduction in the number of nodules. In addition, a fol- low up whole body bone scan also showed an absence of the previous hot uptakes of the ribs, sternum and a reduced uptake of the skull lesion

first, a rapid expansion of the hepatic and skull masses induced necrosis of the tumors or a portal vein occlusion. Second, radiation therapy toward the skull mass induced a delayed abscopal phe- noumenon that reduced the remote original hepatic masses. Third, the ingestion of Phellinus linteus and/or radiation therapy may have affected the regression pro- cess simultaneously or separately by immunological modulation due to some unknown mechanisms.

Ten months after radiation therapy, the follow-up CT revealed a marked reduction in the size of the hepatic mass and a reduction in the number of nodules. In addition, a fol- low up whole body bone scan also showed an absence of the previous hot uptakes of the ribs, sternum and a reduced uptake of the skull lesion

Nishijima, 2009⁵⁰

86-year-old woman with cirrhosis caused by hepatitis C virus

liver

A repeat ultrasound study after 4 months showed that the tumor had decreased in size to less than 4 cm in diameter and that her serum des-g-carboxy prothrombin level had decreased from 678 mAU/ml to 27 mAU/ml. Histologic evaluation of a percutaneous liver biopsy showed extensive necrosis with only a few residual tumor cells.

infarction of tumor tissue because of thrombosis or vasculitis in small ARTeries that supply blood to the tumor. Another possible mechanism is immunologic activation

A repeat ultrasound study after 4 months showed that the tumor had decreased in size to less than 4 cm in diameter and that her serum des-g-carboxy prothrombin level had decreased from 678 mAU/ml to 27 mAU/ml. Histologic evaluation of a percutaneous liver biopsy showed extensive necrosis with only a few residual tumor cells.

Ohta, 2005⁵¹

74-year-old man

Liver

abdominal CT 17 days after endoscopic therapy showed a decrease (5 cm in diameter) of the main tumor in the liver, a marked decrease in the degree of early enhance- ment, and an increase in the nonenhancing area of the tumor (Fig. 2). The small lesion on Cantlie line was no longer visualized, and PIVKA-II levels return to normal values. On September 22, 2003, laparotomy was conducted; the small intrahepatic metastasis on Cantlie line could not be visualized even by intraoperative ultrasonography Microscopic examination demonstrated that the entire tumor had undergone coagulation necrosis. some vessels feeding the tumor were thickened and occluded due to arterial sclerosis

necrosis secondary to severe cholangitis after choledocholithiasis.

abdominal CT 17 days after endoscopic therapy showed a decrease (5 cm in diameter) of the main tumor in the liver, a marked decrease in the degree of early enhance- ment, and an increase in the nonenhancing area of the tumor (Fig. 2). The small lesion on Cantlie line was no longer visualized, and PIVKA-II levels return to normal values. On September 22, 2003, laparotomy was conducted; the small intrahepatic metastasis on Cantlie line could not be visualized even by intraoperative ultrasonography Microscopic examination demonstrated that the entire tumor had undergone coagulation necrosis. some vessels feeding the tumor were thickened and occluded due to arterial sclerosis

Oquinena, 2009⁵²

4-year-old male had a diagnosis of hepatitis B virus- related liver cirrhosis with complete portal vein thrombosis in 1989.

liver

No lesion was detected on CT performed on May 2000 when AFP was slightly elevated.

disturbance in hepatic circulation associated with portal vein thrombosis

No lesion was detected on CT performed on May 2000 when AFP was slightly elevated.

Oquinena, 2009⁵²

61-year-old male had a diagnosis of alcoholic liver cir- rhosis with portal hypertension thrombosis in April 2002

liver

In July 2005, CT scan showed complete remission and normal AFP

disturbance in hepatic circulation associated with portal vein thrombosis

In July 2005, CT scan showed complete remission and normal AFP

Oquinena, 2009⁵²

60-year-old male, diagnosed with familiar hemochromatosis in 2000

liver

In June 2004, MRI scan showed a clear, nonmeasurable volume regression of the tumoral thrombus that was confirmed in October 2004 when a new MRI scan failed to show any distinct focal liver lesion and AFP was normal.

disturbance in hepatic circulation associated with portal vein thrombosis

In June 2004, MRI scan showed a clear, nonmeasurable volume regression of the tumoral thrombus that was confirmed in October 2004 when a new MRI scan failed to show any distinct focal liver lesion and AFP was normal.

Park, 2009⁵³

57-year-old man, hepatitis B virus-related chronic hepatitis over a period of 5 years

liver

Histologically, Frequent apoptosis, necrosis, or acidophilic degeneration of HCC cells was observed

local immune reactions

Histologically, Frequent apoptosis, necrosis, or acidophilic degeneration of HCC cells was observed

Pectasides, 2016⁵⁴

53-year-old man, history of hepatitis C and alcoholic cirrhosis

liver + lung mets + IVC thrombus

In December 2009 There was persistent left portal vein thrombosis as well as hepatic vein thrombosis, and the previously seen pulmonary nodules had either decreased in size or resolved. abdominal ultrasound prior to the scheduled liver biopsy did not show a definitive lesion, and the plan for biopsy was aborighted. in March 2010 CT chest at that time revealed resolution of the pulmonary nodules and hilar lymphadenopathy. Follow-up imaging showed no evidence of disease in the liver or lung parenchyma; however, the tumor thrombus persisted.

tumor ischemia in the setting of portal vein thrombosis + immune response

In December 2009 There was persistent left portal vein thrombosis as well as hepatic vein thrombosis, and the previously seen pulmonary nodules had either decreased in size or resolved. abdominal ultrasound prior to the scheduled liver biopsy did not show a definitive lesion, and the plan for biopsy was aborighted. in March 2010 CT chest at that time revealed resolution of the pulmonary nodules and hilar lymphadenopathy. Follow-up imaging showed no evidence of disease in the liver or lung parenchyma; however, the tumor thrombus persisted.

Peddu, 2008⁵⁵

baby of a 32-year-old female

liver

Between 6 and 18 months the tumour gradually regressed in size, and US at 2 years of age found no evidence of tumour

Between 6 and 18 months the tumour gradually regressed in size, and US at 2 years of age found no evidence of tumour

Peddu, 2008⁵⁵

32-year-old woman, She had given birth 4 years before and had thereafter been taking an oral contraceptive containing 0.25 mg d-norgestrel and 0.05 mg ethinyl oestradiol

liver

MRI with manganese performed 18 months after initial presentation demonstrated a marked reduction in the size of the adenoma, which measured 24 mm. further follow-up MRI at 4 years demonstrated a normal liver with complete resolution of the tumour

MRI with manganese performed 18 months after initial presentation demonstrated a marked reduction in the size of the adenoma, which measured 24 mm. further follow-up MRI at 4 years demonstrated a normal liver with complete resolution of the tumour

Peddu, 2008⁵⁵

57-year-old man

Liver

7 weeks later, a CT demonstrated a larger central area of necrosis within the HCC. Two months later, at a clinic visit, an alpha-fetoprotein value was markedly reduced at 87 ng/dl. A CT examination showed no evidence of HCC

auto- infarction

7 weeks later, a CT demonstrated a larger central area of necrosis within the HCC. Two months later, at a clinic visit, an alpha-fetoprotein value was markedly reduced at 87 ng/dl. A CT examination showed no evidence of HCC

Peddu, 2008⁵⁵

74-year-old man

liver

Histological examination of a biopsy specimen of the mass. demonstrated infarcted liver tissue and inflamed granulation tissue containing macrophages and m-year-old femaleibroblasts. There was no evidence of malig- nancy and no pathogens were identified. CT 5 months thereafter demonstrated a normal liver with no evidence of mass.

Histological examination of a biopsy specimen of the mass. demonstrated infarcted liver tissue and inflamed granulation tissue containing macrophages and m-year-old femaleibroblasts. There was no evidence of malig- nancy and no pathogens were identified. CT 5 months thereafter demonstrated a normal liver with no evidence of mass.

Peddu, 2008⁵⁵

54-year-old woman

Biliary system

microscopy of a CT-guided biopsy specimen found no evidence of malignancy. Repeat CT-guided biopsy and laparoscopic biopsy followed; histological examination demonstrated infiltration of the liver parenchyma and bile duct wall by mixed inflammatory cells. CT performed 6 months after laparoscopy showed marked regression in the volume of the central hepatic lesion

microscopy of a CT-guided biopsy specimen found no evidence of malignancy. Repeat CT-guided biopsy and laparoscopic biopsy followed; histological examination demonstrated infiltration of the liver parenchyma and bile duct wall by mixed inflammatory cells. CT performed 6 months after laparoscopy showed marked regression in the volume of the central hepatic lesion

Randolph, 2008⁵⁶

56-year-old Caucasian man, chronic HCV infection for 2 years. History of emphysema, hypertension, and gastroesophageal reflux. tattoo 7 years before. 40 pack-year history of smoking and had consumed five to six beers daily for 40 years. carpenter

Liver

35 days later, the previously palpated mass had resolved. A complete blood count was normal, and AFP had returned to normal

exaggerated immune response or a compromised tumoral blood supply could explain the regression

35 days later, the previously palpated mass had resolved. A complete blood count was normal, and AFP had returned to normal

Rene, 1992⁵⁷

67-year-old male. Cirrhosis

Liver

2 years later AFP returned no normal values. US and CT didn't show any masses.

Ischemia

2 years later AFP returned no normal values. US and CT didn't show any masses.

Sibartie, 2008⁵⁸

76-years-old man, history of heavy alcohol intake

Liver

CT scan revealed that the liver mass had decreased in size, with an interval change in maximum axial diameter from 6 cm to 3.3 cm and that the two other lesions had disappeared.

autoembolization

CT scan revealed that the liver mass had decreased in size, with an interval change in maximum axial diameter from 6 cm to 3.3 cm and that the two other lesions had disappeared.

Stefanczyk-Sapieha, 2008⁵⁹

56-year-old man, chronic alcohol abuse, hepatitis C, type 2 diabetes, heavy smoking, depression, and antisocial patterns of behaviour

Liver

MRI of the abdomen was repeated and results were compared with previous findings. A shrunken cirrhotic liver was found, with evi- dence of portal venous hypertension, including splenomegaly and ascites. The previously identi- fied enhancing areas of the left lobe of the liver, suspicious for HCC, were no longer present.

MRI of the abdomen was repeated and results were compared with previous findings. A shrunken cirrhotic liver was found, with evi- dence of portal venous hypertension, including splenomegaly and ascites. The previously identi- fied enhancing areas of the left lobe of the liver, suspicious for HCC, were no longer present.

Stoelben, 1998⁶⁰

56-year-old male, psoriasis, gout, diabetes mellitus type II b, essential hypertension, reflux esophagitis II0 with a hiatal hernia, and a state after traumatic fracture of the right ribs 6 to 9 in 1989

Liver

Another puncture of the focus was performed. At this time the tumor was 4 cm in diameter. Histologic assessment of the specimens from both tumors showed a mainly necrotic, multivocal, highly differentiated, trabecular-like HCC with a connective tissue-like pseudocapsule

tumor regression due to immune stim- ulation

Another puncture of the focus was performed. At this time the tumor was 4 cm in diameter. Histologic assessment of the specimens from both tumors showed a mainly necrotic, multivocal, highly differentiated, trabecular-like HCC with a connective tissue-like pseudocapsule

Stoelben, 1998⁶⁰

74-year-old male

Liver

US, during second addition, showed tumor size was 2.5 cm. Angiography and staging investigations did not show pathologic findings. Histologic assessment showed totally necrotic tumor tissue with small islets of a clear cell primary liver cell carcinoma, demarcated by granulated tissue rich in foam cells

tumor regression due to immune stim- ulation

US, during second addition, showed tumor size was 2.5 cm. Angiography and staging investigations did not show pathologic findings. Histologic assessment showed totally necrotic tumor tissue with small islets of a clear cell primary liver cell carcinoma, demarcated by granulated tissue rich in foam cells

Storey, 2011⁶¹

52-year-old man, alcohol abuse

Liver + lung mets

Follow up CT scans 6 months later, revealed a decreased in size of the liver lesion to 3.5 cm, and almost complete resolution of the bilateral lung nodules with normal AFP. A CT scan of the chest and abdomen performed 9 months after the initial diagnosis, showed further regression in the size of the hepatic lesion, measuring 2.7 cm in diameter, and no new lung nodules. Pathology evaluation after surgery showed a 1.8 cm nodule with necrosis surrounded by fibrosis.

immune system

Follow up CT scans 6 months later, revealed a decreased in size of the liver lesion to 3.5 cm, and almost complete resolution of the bilateral lung nodules with normal AFP. A CT scan of the chest and abdomen performed 9 months after the initial diagnosis, showed further regression in the size of the hepatic lesion, measuring 2.7 cm in diameter, and no new lung nodules. Pathology evaluation after surgery showed a 1.8 cm nodule with necrosis surrounded by fibrosis.

Takeda, 2000⁶²

68-year-old Japanese man, 7-year history of chronic Hep C, lung lobectomy for tuberculosis for tuberculosis and a blood transfusion. regular drinker, consuming approximately 540 mL of sake daily for 40 years

Liver

1 month after reaching terminal stage, follow-up CT scan showed regression of more than 90%

1 month after reaching terminal stage, follow-up CT scan showed regression of more than 90%

Tsai, 2014⁶³

74-year-old man with chronic hepatitis C-related cirrhosis and end-stage renal disease undergoing maintenance haemodialysis for years

Liver

2.5 years later a CT showed a 2x2x2.5 ring calcification

2.5 years later a CT showed a 2x2x2.5 ring calcification

Ushigome et al., 2007⁶⁴

60 years old male patient, cirrhosis secondary to idiopathic hepatitis

Liver

The aneurysm began to contract after the 34th postoperative day. Then, was not detectable on the 37th postoperative day. It was assumed to have embolized spontaneously.

slow blood flow through the aneurysm

The aneurysm began to contract after the 34th postoperative day. Then, was not detectable on the 37th postoperative day. It was assumed to have embolized spontaneously.

Kogiso et al., 2000⁶⁵

A 50-year-old woman was diagnosed with chronic hepatitis C at the age of 33 years, but IFN therapy was contra-indicated, because she exhibited pancytopenia Transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) was performed on several occasions from the time she was 47 years of age. However, further treatment became difficult because of a lack of spare hepatic capacity

Liver

no HCV-RNA was evident by day 87 post-LT

immunological response

no HCV-RNA was evident by day 87 post-LT

Kogiso et al., 2000⁶⁵

52-year-old man, was diagnosed with chronic HCV infection (serological type 2) at 47 -year-old Was naıve in the context of HCV therapy, because his condition was complicated by ascites and HCC. The cancer could not be treated radically because of his poor liver function

Liver

By day 115 after LT, the HCV RNA status resolved spontaneously, and the patient achieved continuous viral disappearance

immunological response

By day 115 after LT, the HCV RNA status resolved spontaneously, and the patient achieved continuous viral disappearance

L'Huillier, 2024⁶⁶

70-year-old man. alcohol-related cirrhosis

Liver

2 years later, a new CT disclosed tumoral regression of HCCs

immunologic reactions

2 years later, a new CT disclosed tumoral regression of HCCs

Franses, 2021⁶⁷

64-year-old man. History of atrial fibrillation (on a stable dose of a direct oral anticoagulant for years)

Liver

follow-up MRI approximately 9 weeks after the initial MRI showed a decrease in size to 1.6 cm and a decrease in arterial enhancement of the biopsy-proven HCC. The patient was taken to the operating room for a planned resection, at which time the surgeon noted no evidence of tumor at the site predicted by the pre-operative imaging. Instead, only slight dimpling was noted in segment 4a at the expected site.

immunologic reactions

follow-up MRI approximately 9 weeks after the initial MRI showed a decrease in size to 1.6 cm and a decrease in arterial enhancement of the biopsy-proven HCC. The patient was taken to the operating room for a planned resection, at which time the surgeon noted no evidence of tumor at the site predicted by the pre-operative imaging. Instead, only slight dimpling was noted in segment 4a at the expected site.

Ghattu, 2022⁶⁸

64-year-old male

Liver

Several months later, when the patient followed up for his HCC, there was near complete spontaneous regression of the liver masses and lung nodules.

The more peripheral location could predispose the tumor to ischemia, given the more tenuous blood supply, particularly in cirrhotic livers and subcapsular masses. Furthermore, the subcapsular location and potentially local disruption of the capsule may predispose a lesion for immunologic presentation.

Several months later, when the patient followed up for his HCC, there was near complete spontaneous regression of the liver masses and lung nodules.

Ghattu, 2022⁶⁸

65-year-old male. History of cirrhosis due to chronic HCV infection

Liver

Over the course of 15 months in hospice, the patient made significant functional gains. This unexpected recovery prompted an AFP recheck, which revealed a significant reduction. A CT scan showed a reduction in infiltrative disease with near complete resolution of the massive infiltrative right hepatic lobe mass

The more peripheral location could predispose the tumor to ischemia, given the more tenuous blood supply, particularly in cirrhotic livers and subcapsular masses. Furthermore, the subcapsular location and potentially local disruption of the capsule may predispose a lesion for immunologic presentation.

Over the course of 15 months in hospice, the patient made significant functional gains. This unexpected recovery prompted an AFP recheck, which revealed a significant reduction. A CT scan showed a reduction in infiltrative disease with near complete resolution of the massive infiltrative right hepatic lobe mass

Ghattu, 2022⁶⁸

57-year-old female. History of cirrhosis due to HCV infection and prior HCC in remission, treated with surgical wedge resection three years prior to presentation

Liver

Repeat imaging prior to a planned hepatic angiogram showed spontaneous regression of the 2 cm LI-RADS 5 lesion. AFP had also decreased from 27.2 ng/mL to 5.5 ng/mL.

The more peripheral location could predispose the tumor to ischemia, given the more tenuous blood supply, particularly in cirrhotic livers and subcapsular masses. Furthermore, the subcapsular location and potentially local disruption of the capsule may predispose a lesion for immunologic presentation.

Repeat imaging prior to a planned hepatic angiogram showed spontaneous regression of the 2 cm LI-RADS 5 lesion. AFP had also decreased from 27.2 ng/mL to 5.5 ng/mL.

Costa-Santos, 2020⁶⁹

68-year-old Caucasian man. History of chronic hepatitis C virus (HCV) infection, genotype 1b, in the context of blood transfusion in 1977. History of prostatic adenocarcinoma and underwent surgery and radiotherapy.

liver

Ten months later, AFP markedly decreased (28ng/mL), and abdominal MRI showed decreasing size, number, and vascularisation of lesions previously described

A. muricata compounds have cytotoxic activity against liver cancer cells

Ten months later, AFP markedly decreased (28ng/mL), and abdominal MRI showed decreasing size, number, and vascularisation of lesions previously described

Sonabre, 2020⁷⁰

74-year-old white male. History of obesity, type 2 diabetes, dyslipidemia, hypertension, hypothyroidism, and prostatism. He had coronary artery stenoses requiring bypass grafting and also had a cholecystectomy. His medications included aspirin, amlodipine, metoprolol, atorvastatin, insulin, metformin, ferrous sulfate, finasteride, and levothyroxine.

Liver

One year after the initial diagnosis, a contrast-enhanced abdominal CT showed large ascites, nodular liver, a 2.5-cm ill-defined, non-enhancing right hepatic lobe lesion and resolution of expansile right portal and main portal vein thrombus. Repeat testing showed persistently normal serum AFP levels.

likely involved vascular phenomena and immunologic pathways

One year after the initial diagnosis, a contrast-enhanced abdominal CT showed large ascites, nodular liver, a 2.5-cm ill-defined, non-enhancing right hepatic lobe lesion and resolution of expansile right portal and main portal vein thrombus. Repeat testing showed persistently normal serum AFP levels.

Singh, 2022⁷¹

43-year-old man. History of alcohol-associated cirrhosis, type 2 diabetes, and hypertension

Liver

Surveillance MRI revealed a tumor reduction to 0.9 x 0.9 cm, suggestive of HCC autoinfarction

it is possible that the tumor regressed because of it outgrowing its blood supply

Surveillance MRI revealed a tumor reduction to 0.9 x 0.9 cm, suggestive of HCC autoinfarction

Singh, 2022⁷¹

54-year-old man. History of cirrhosis due to hepatitis B. HCC found in segment 7 and treated successfully with transarterial chemoembolization 4 months before presentation

Liver

One month later, a triple-phase computed tomography scan showed tumor shrinkage to 4.5 x 3.2 cm, suggestive of autoinfarction

it is possible that the tumor regressed because of it outgrowing its blood supply

One month later, a triple-phase computed tomography scan showed tumor shrinkage to 4.5 x 3.2 cm, suggestive of autoinfarction

Xu, 2023⁷²

81-year-old female. History of chronic active hepatitis B. She had been taking the antiviral drug entecavir. Past medical history included hypertension, diabetes, and type B aortic dissection, which were all medically managed. Family history was significant for colon cancer in one of her sons.

Lung, Liver

On a routine follow-up 5 months from RFA, she reported feeling well with greatly improved symptoms. CT at that time showed significant decrease in size of the multiple lung nodules and the liver masses. Repeat CT scans 8 months and 14 months after RFA again showed further decrease in the size of the lung lesions.

self-anti-tumor immune response

On a routine follow-up 5 months from RFA, she reported feeling well with greatly improved symptoms. CT at that time showed significant decrease in size of the multiple lung nodules and the liver masses. Repeat CT scans 8 months and 14 months after RFA again showed further decrease in the size of the lung lesions.

Kimura, 2021⁷³

84-year-old Japanese female with hepatitis C virus (HCV)-associated chronic hepatitis and diabetes mellitus treated with insulin

Liver

Small nodules were entirely composed of necrotic tissue, and a thick trabecular pattern could be recognized by reticulin staining, indicating moderately differentiated HCC with extensive coagulative necrosis, existing in a nodule-in-nodule pattern.

the immune reaction might have played an important role

Small nodules were entirely composed of necrotic tissue, and a thick trabecular pattern could be recognized by reticulin staining, indicating moderately differentiated HCC with extensive coagulative necrosis, existing in a nodule-in-nodule pattern.

Kawaguchi, 2019⁷⁴

A 56-year-old (at first presentation) Japanese man. History of hepatitis C virus (HCV)-related liver cirrhosis and type 2 DM (750 mg/day of metformin and 1 mg/day of glimepiride).

Liver

Ten weeks since the initiation of SGLT2i treatment, angiography of the hepatic artery revealed no tumor staining. Tumor staining was also not seen in angiography of the collateral arteries. Furthermore, in contrast-enhanced computed tomography scan, the arterial phase hyperenhancement of the contrast agent within the mass disappeared. Moreover, blood biochemical examination showed that the elevated serum AFP level decreased within normal limits, indicating spontaneous regression of HCC

Since insulin resistance is a potent risk factor for HCC proliferation 13, SGLT2i may suppress HCC through an improvement of insulin resistance.

Ten weeks since the initiation of SGLT2i treatment, angiography of the hepatic artery revealed no tumor staining. Tumor staining was also not seen in angiography of the collateral arteries. Furthermore, in contrast-enhanced computed tomography scan, the arterial phase hyperenhancement of the contrast agent within the mass disappeared. Moreover, blood biochemical examination showed that the elevated serum AFP level decreased within normal limits, indicating spontaneous regression of HCC

Koya, 2018⁷⁵

83-year-old man with hepatitis C virus infection. He had received a diagnosis of HCC and had been treated by radiofrequency ablation and transcatheter arterial chemoembolization (TACE) since the age of 74 years. past medical history of hypertension, diabetes mellitus, and benign prostatic hyperplasia at 60 years of age and cerebral infarction at 72 years of age He had been receiving oral treatment with diuretics and a preparation of branched chain amino acid

Liver

His general condition gradually improved. A CT scan 16 months after the last TACE revealed the disappearance of the thrombus of the left branch of the portal vein and atrophic change of the left lobe. The tumor thrombus in the main portal vein and the tumors in the left lobe also disappeared

The massive main portal vein tumor thrombus decreased portal blood flow, and the arterioportal shunt decreased blood supply from the hepatic artery to the tumors. These disturbances of the blood circulation could have induced hypoxia of rapidly increased tumors and precipitated a tumor regression

His general condition gradually improved. A CT scan 16 months after the last TACE revealed the disappearance of the thrombus of the left branch of the portal vein and atrophic change of the left lobe. The tumor thrombus in the main portal vein and the tumors in the left lobe also disappeared

Hirata, 2025⁷⁶

73-year-old Japanese woman with untreated chronic hepatitis C. Smoking history of 37.5 pack-years

Liver

Seven months after the initial diagnosis revealed marked regression of the hypervascular HCC. The tumor thrombus in the left branch of the main portal vein had disappeared. Her tumor markers were notably reduced.

the tumor thrombus in the left branch of the main portal vein likely caused ischemia and subsequent necrosis of the tumor. Furthermore, the patient’s decision to quit smoking may have reduced oxidative stress and enhanced their natural immune responses against the tumor, contributing to SR. These findings suggest that both tumor hypoxia and immune activation may have played critical roles in the SR

Seven months after the initial diagnosis revealed marked regression of the hypervascular HCC. The tumor thrombus in the left branch of the main portal vein had disappeared. Her tumor markers were notably reduced.

Chohan, 2019⁷⁷

79-year-old Chinese female. History of chronic hepatitis C and well-controlled essential hypertension, for which she took valsartan 80 mg once daily

Liver, Lung

At two months follow-up CT, the lung lesions had completely disappeared, and there was a significant decrease in the size of the primary liver lesion. Serum AFP levels had fallen to almost within the normal range

None reported

At two months follow-up CT, the lung lesions had completely disappeared, and there was a significant decrease in the size of the primary liver lesion. Serum AFP levels had fallen to almost within the normal range

Ishii-Kitano, 2022⁷⁸

70-year-old woman. 10-year history of primary biliary cholangitis (PBC) and reumathoid arthirtis (RA)

Liver

After two months of observation, the tumors spontaneously regressed and nearly vanished

None reported

After two months of observation, the tumors spontaneously regressed and nearly vanished

Shishimoto, 2023⁷⁹

71-year-old man. He had undergone drug-eluting stent grafting to the coronary arteries for angina pectoris 4 years before and had been receiving MTX (12 mg p.o. once a week) to treat his rheumatoid arthritis for more than 6 years

liver

Enhanced CT 2 months after discharge showed complete disappearance of small EHE lesions and marked shrinkage of large EHE lesions. Follow-up CT taken 12 months after the biliary drainage showed complete regression of the liver EHE lesions

Anti-icteric therapy might have contributed to the spontaneous regression of the multiple liver EHEs through biliary decompression.

Enhanced CT 2 months after discharge showed complete disappearance of small EHE lesions and marked shrinkage of large EHE lesions. Follow-up CT taken 12 months after the biliary drainage showed complete regression of the liver EHE lesions

Oshima, 2025⁸⁰

67-year-old man. Medical history of Sjögren’s syndrome and psoriasis with no active treatment and hypothyroidism with levothyroxine supplementation. Smoker of 1 pack of cigarettes per day for more than 40 years.

liver, lung, pancreas

PET/CT 3 weeks after admission showed that the multiple masses spontaneously regressed. A week later, a biopsy of the liver mass, which had decreased in size from 45 to 30 mm, revealed extensive necrosis in most areas of the mass and low Ki-67 expression. At the fourmonth follow-up, the masses continued to regress, with some completely disappearing following smoking cessation and watchful waiting

Smoking cessation can contribute to the improvement of the tumor microenvironment, possibly leading to reactivation of immune cells and tumor regression

PET/CT 3 weeks after admission showed that the multiple masses spontaneously regressed. A week later, a biopsy of the liver mass, which had decreased in size from 45 to 30 mm, revealed extensive necrosis in most areas of the mass and low Ki-67 expression. At the fourmonth follow-up, the masses continued to regress, with some completely disappearing following smoking cessation and watchful waiting

Meares, 1979⁸¹

The patient is a 64-year-old man, himself a professional in psychological healing.

In two weeks he reported the first signs of improvement. In six weeks he was able to discontinue the use of the enema, and had regained the use of his bowels to the extent of passing stools which he described as like a pencil. In two months he was sleeping the night through without getting up. At this stage he was extremely confident that he had beaten the growth, and he went for a month’s holiday to another State.

The extreme reduction of anxiety in these patients triggers off the mechanism as that which becomes active in the rare spontaneous remissions. This would be consistent with the observation that spontaneous remissions are often associated with some kind of religious experience or profound psychological reaction.

In two weeks he reported the first signs of improvement. In six weeks he was able to discontinue the use of the enema, and had regained the use of his bowels to the extent of passing stools which he described as like a pencil. In two months he was sleeping the night through without getting up. At this stage he was extremely confident that he had beaten the growth, and he went for a month’s holiday to another State.

Andrén & Frieberg et al., 1956⁸²

5-year-old girl, had blood in the stools for 3 weeks

The remaining polyp had clearly decreased in size and then measured 6 x 6 millimeters and, six months later, at a further control examination, it had decreased still more, the measurement then being 4 x 3 millimeters

The remaining polyp had clearly decreased in size and then measured 6 x 6 millimeters and, six months later, at a further control examination, it had decreased still more, the measurement then being 4 x 3 millimeters

Andrén & Frieberg et al., 1956⁸²

Girl aged 5 1/2 years, had bleeding from the rectum for a year

Eighteen months later, on control examination, the polyp had clearly decreased in size; it then measured 7 x 7 millimeters

Eighteen months later, on control examination, the polyp had clearly decreased in size; it then measured 7 x 7 millimeters

Gottfried et al., 1982⁸³

A 65-year-old alcoholic black man, retired manual laborer in a spark plug factory

Jaundice resolved, no evidence of tumor demonstrable by radionuclide scanning or laparoscopic liver biopsy, liver scan normal, alphafetoprotein negative

Abstention from alcohol

Jaundice resolved, no evidence of tumor demonstrable by radionuclide scanning or laparoscopic liver biopsy, liver scan normal, alphafetoprotein negative

Lam et al., 1982⁸⁴

A 50-year-old male carpenter from Southern China

epigastric distension decreased, liver decreased progressively in size, fluid retention disappeared, no clinical evidence of HCC, minimal biochemical abnormalities, no dysplasia, no clinical or biochemical evidence of liver cirrhosis, no feature of residual HCC, asymptomatic, and apparently free from recurrence

regression of HCC might occur by involution rather than maturation, regressed HCC might be replaced by surrounding tissue instead of leaving behind dysplasia

epigastric distension decreased, liver decreased progressively in size, fluid retention disappeared, no clinical evidence of HCC, minimal biochemical abnormalities, no dysplasia, no clinical or biochemical evidence of liver cirrhosis, no feature of residual HCC, asymptomatic, and apparently free from recurrence

Sato et al., 1985⁸⁵

78-year-old Japanese man with chronic liver disease, no history of alcoholic ingestion

Tumors disappeared with normalization of the alphafetoprotein level, the radiolucent area around the fracture site of the femur became consolidated

Tumors disappeared with normalization of the alphafetoprotein level, the radiolucent area around the fracture site of the femur became consolidated

Ayres et al., 1990⁸⁶

63-year-old white woman, no relevant past history or family history, no previous history of jaundice or hepatitis, no excessive alcohol intake, no previous operations or blood transfusions, no drugs, recent weight loss

Asymptomatic after five months, weight gain, cleared metastases, considerable shrinkage of the tumour, cryptogenic macronodular cirrhosis with no evidence of carcinoma in repeat biopsy, normal liver function tests after twelve months

Asymptomatic after five months, weight gain, cleared metastases, considerable shrinkage of the tumour, cryptogenic macronodular cirrhosis with no evidence of carcinoma in repeat biopsy, normal liver function tests after twelve months

Morley, 1947⁸⁷

a woman, aged 48

I could no longer feel the growth at the ampulla

I could no longer feel the growth at the ampulla

Mcsweeney et al., 1973⁸⁸

A 5 1/2-month-old white boy

Liver had decreased remarkably in size two years after surgery, development of dense mottled calcification in the right lobe of the liver at 21 months of age, increase in the density of the calcifications at age 8 years, contraction and increased density in the right upper quadrant calcifications in adulthood

Liver had decreased remarkably in size two years after surgery, development of dense mottled calcification in the right lobe of the liver at 21 months of age, increase in the density of the calcifications at age 8 years, contraction and increased density in the right upper quadrant calcifications in adulthood

Pardes et al., 1982⁸⁹

A 7 1/2-month-old healthy white male infant

On a follow-up examination eight months later, the hepatomegaly had improved markedly. The abdominal girth was noted to be 49 centimeters. Many of the previously noted lesions had disappeared, and those that remained were much less obvious.

Spontaneous regression

On a follow-up examination eight months later, the hepatomegaly had improved markedly. The abdominal girth was noted to be 49 centimeters. Many of the previously noted lesions had disappeared, and those that remained were much less obvious.

Penkava & Rothenberg et al., 1981⁹⁰

55-year-old woman, had been on norethynodrel with mestranol (Envois®, G. D. Searle & Co., Chicago, Illinois), 5 mg/day, for about 10 years without interruption

spontaneous regression of the lesion

spontaneous regression of the lesion

Buhler et al., 1982⁹¹

32-year-old woman, history of oral contraceptive use (norgestrel 0.25 milligrams, ethinyl estradiol 0.05 milligrams) for 6 years

Discontinuation of contraceptives led to symptom relief within a few weeks, normal physical examination of the liver in June 1978 and September 1979, normal liver enzymes, no evidence of residual tumor in technetium scan and ultrasonography of the liver in September 1979

Discontinuation of contraceptives led to symptom relief within a few weeks, normal physical examination of the liver in June 1978 and September 1979, normal liver enzymes, no evidence of residual tumor in technetium scan and ultrasonography of the liver in September 1979

Abiru et al., 2002⁹²

Heianna et al., 2007⁹³

Herreros-Villanueva et al., 2012⁹⁴

Hirakawa et al., 2009⁹⁵

Jeon et al., 2005⁹⁶

Rizell et al., 2005⁹⁷

Vardhana et al., 2007⁹⁸

Parks et al.⁹⁹

Sawada et al.¹⁰⁰

Choi et al., 2010¹⁰¹

Iijima et al., 2001¹⁰²

Inui et al., 2005¹⁰³

Jerraya et al., 2011¹⁰⁴

Laumonier et al., 2010¹⁰⁵

Levy et al., 2001¹⁰⁶

Pohl et al., 2000¹⁰⁷

Volkmann et al., 2008¹⁰⁸

Huz et al., 2012¹⁰⁹

Hsiao et al., 2008¹¹⁰

Tovo, 2024¹¹¹

Tovo et al., 2024¹¹¹

(2009)¹¹²