Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization.

BACKGROUND/AIM: We examined tumor marker levels to assess in more detail transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We enrolled patients treated from 2000 to 2011 for HCC beyond the Milan criteria who had good hepatic reserve function (Child-Pugh A) and no portal vein thrombosis or metastases (n = 154). The modified criteria for being TACE-refractory according to the Liver Cancer Study Group of Japan (m-LCSGJ), from which the tumor marker item was excluded, and the Assessment for Retreatment with TACE (ART) score were used for determining whether the HCC was TACE refractory. α-Fetoprotein ≥ 100 ng/ml, fucosylated α-fetoprotein ≥ 10%, and des-gamma-carboxy prothrombin ≥ 100 mAU/ml were used to define whether tumor markers were positive. We added up the number of positive tumor markers as a prognostic score to assess in more detail the evaluation of TACE-refractory HCC. RESULTS: In order to divide the patients into a refractory and nonrefractory group, the m-LCSGJ criteria [mean survival time (MST) 27.1 vs. 49.9 months; p < 0.001] were superior to the ART score (MST 22.0 vs. 35.1 months; p = 0.051). In the refractory group according to the m-LCSGJ criteria, the patients with a low score of positive tumor markers (<2) after 2 sessions of TACE (n = 36) showed a better prognosis than the others (n = 72) (MST 37.7 vs. 23.2 months; p = 0.014). CONCLUSION: Patients being nonrefractory according to the m-LCSGJ criteria had a better response, and using the number of tumor markers (≥ 2) is an easy method for predicting the response to TACE and for a more detailed evaluation of TACE-refractory HCC.

Real-time tissue elastography: non-invasive evaluation of liver fibrosis in chronic liver disease due to HCV.

BACKGROUND/AIMS: We evaluated the diagnostic efficacy for advanced fibrosis of real-time tissue elastography (RTE), is a newly introduced non-invasive method, in hepatitis C virus (HCV) patients. METHODOLOGY: Sixty-six chronic liver diseases with HCV (CLD-HCV) were evaluated by RTE, FIB-4, and APRI, as well as biopsy or hepatectomy findings. Seventeen healthy volunteers, and 1 with elevation of transaminase and 5 with liver tumors within their normal liver were enrolled for normal controls. Severe fibrosis was defined as METAVIR score 3 or 4. The tissue elasticity value was expressed by LF-index created by the program incorporated in the ultrasound device. The percentage of fibrosis area in each specimen (%FA) was determined with a personal computer. A receiver operating characteristic curve (ROC) was calculated for each non-invasive method of estimation of fibrosis. RESULTS: The values for the area under the ROC for LF-index, APRI, and FIB-4 were 0.88, 0.81, and 0.84, respectively. Accuracy, sensitivity, and specificity for prediction of LF-index (>2.8) for severe fibrosis were 86.5%, 78.6%, and 93.6%, respectively, which were better than those of FIB-4 and APRI. LF-index showed a good relationship to %FA (r=0.276, P=0.020). CONCLUSION: RTE is an effective method for predicting severe fibrosis in CLD-HCV.

Recent trends of Japanese hepatocellular carcinoma due to HCV in aging society.

BACKGROUND/AIMS: The mean age of hepatocellular carcinoma (HCC) patients has increased (=65 years old). We want to identify the recent trend of the clinical features of HCC patients due to hepatitis C virus (HCV) (HCV-HCC). METHODOLOGY: From 2000 to 2009, 855 naive HCC patients were admitted. HCV-HCC patients were divided into two groups, first period group (2000-04, n=270) and second period group (2005-09, n=343) and the clinical features of HCV-HCC were investigated. RESULTS: There was no difference in gender, TNM stage and percentages of HCV-HCC between the periods. On the other hand, the ratio of HCV-HCC patients with worse liver function (Child-Pugh B or C), elderly (=75 years old) and the population of patients treated with low invasive radiofrequency ablation were increased (30.0% to 42.0%, 17.2% to 35.8% and 25.1% to 36.2%, respectively; p<0.01). The 1y-, 3y- and 5y-survival rate of HCV-HCC did not show differences (82.1%, 60.5% and 44.7% vs. 81.8%, 56.9% and 37.7%, respectively; p=0.219). CONCLUSIONS: The ratio of aged HCV-HCC as well as HCV-HCC patients with worse liver function was increased. The less invasive treatment for HCC in these patients and the quick anti-viral treatment for HCV patients should be considered to avoid occurrence of HCC in Japan.

Hepatic resection assisted by ablative therapy for advanced hepatocellular carcinoma.

BACKGROUND/AIMS: We attempted combinations of resection and ablative therapies (ethanol injection (EI) or radiofrequency therapy (RFA)) in hepatocellular carcinoma (HCC) patients. METHODOLOGY: Thirty-one patients with naive HCC treated from January 2000 to June 2010 were enrolled. All were tumor node metastasis stage III and the number of tumors was countable (< or = 5). Twelve were treated with resection assisted with an ablative therapy (combination group) and 19 with resection only (resection group). Clinical backgrounds and prognosis were investigated. RESULTS: The total scores for up-to-seven criteria were larger in the combination group than in the resection group (p=0.01), while other clinical background findings were not significantly different between the groups. In the combination group, 10 cases underwent resection combined with RFA and 2 with EI. The 1- and 3-year survival rates were not significantly different between the groups (combination group, 88.2% and 88.2%, respectively; resection group, 90.9% and 80.8%, respectively). There were no severe complications. CONCLUSION: Our results indicate that combination therapy is a therapeutic option for cases with countable HCCs who are difficult to treat by resection only.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.

BACKGROUND AND AIM: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (> or = 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. METHODS: Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; > or = 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. RESULTS: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 +/- 3.2 vs 64.2 +/- 7.5 years, 676.3 +/- 2643.7 vs 142.4 +/- 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. CONCLUSIONS: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.

Diagnostic value of sonazoid for hepatic metastasis: comparison with FDG PET/CT.

BACKGROUND/AIMS: This study was conducted to evaluate the diagnostic efficacy of contrast enhanced ultrasonography (CEUS) with perflubutane (Sonazoid) for hepatic metastasis and compared it with that of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT). METHODOLOGY: From January 2007 to July 2009, 109 Japanese patients with gastrointestinal tract cancer were enrolled, of whom 4 had esophageal cancer, 28 gastric cancer, 1 duodenal cancer, and 76 colorectal cancer. After a bolus injection with Sonazoid (0.5 ml/body), the liver was scanned in both arterial and Kupffer phases. The results of PET/CT and other abdominal imaging examinations were not shown to the CEUS operators. We compared diagnostic efficacy between CEUS and PET/CT. RESULTS: Average values for age, body mass index, and maximum diameter of the hepatic metastasis were 68.7 +/- 11.0 years, 21.2 +/- 4.2, and 29.2 +/- 20.5mm, respectively. Hepatic metastasis were suspected in 31 patients based on PET/CT findings and 32 by CEUS. Finally, hepatic metastasis was diagnosed in 30 patients. The sensitivity, specificity, and accuracy rates for CEUS and PET/CT were similar (100% vs. 100%, 97.5% vs. 98.7%, and 95.5% vs. 93.6%, respectively). CONCLUSION: CEUS had a diagnostic value similar to that of PET/CT for hepatic metastasis.

Risk factors for death in 224 cases of hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been reported as effective therapy for unresectable hepatocellular carcinoma (HCC), however, few have described methods for predicting prognosis, especially in patients treated by repeated TACE. To determine risk factors for death and try to predict the prognosis, we evaluated clinical data. METHODOLOGY: We retrospectively analyzed the clinical parameters of 224 patients with unresectable HCC treated with repeated TACE from January 1997 to December 2007. TACE was repeated when recurrence was diagnosed by tumor marker elevation and/or dynamic computed tomography findings. Factors affecting survival were evaluated using multivariate analysis after univariate analysis. Next, we combined the score for each significant factor into a single prognostic score and added up the positive factors in each case, then analyzed the significance of prognosis, after which the results were compared with other prognostic scoring systems. RESULTS: Multivariate analysis revealed that bilobular HCC, alpha-fetoprotein (> or = 400 ng/ml), tumor invasion of the portal vein, tumor size (> or = 10 cm), and albumin (< 2.8 g/dl) were related to poor prognosis, and developed a prognostic scoring system from those. According to that score, patients were classified into 5 groups. CONCLUSION: Our scoring system was easily performed and the results showed that repeated TACE should not be administered to patients with scores of 3 or more.

Efficacy of radiofrequency ablation therapy compared to surgical resection in 164 patients in Japan with single hepatocellular carcinoma smaller than 3 cm, along with report of complications.

BACKGROUND/AIMS: Radiofrequency ablation therapy (RFA) has become widely used against hepatocellular carcinoma (HCC), mainly because of its ease of use, lower level of invasiveness, and high level of effectiveness. To compare the efficacy and safety of RFA with surgery, we retrospectively investigated relevant patient clinical data. METHODOLOGY: The patients with a single HCC (3 cm > or =, Child-Pugh A or B) who were treated with RFA (RFA-group: n=105) or surgery (Surgery-group: n=59) from January 2000 to June 2007 were enrolled. RESULTS: The ratio of patients classified as Child-Pugh B was greater in RFA-group (24.8% vs. 8.5%, P=0.011), though the sizes of the tumors were not significantly different. There were no significant differences for survival rates or disease free survival rates after 3- and 5-years (RFA-group vs. Surgery-group; survival: 87.8 and 59.3% vs. 91.4 and 59.4%, disease free survival: 58.7 and 24.6% vs. 64.3 and 22.4%, respectively). As for complications, in RFA-group there was no severe complication while there was 1 case of postoperative hepatic failure death and 2 with a postoperative abscess in Surgery-group. CONCLUSIONS: In the present study, patients with a single HCC smaller than 3cm who underwent RFA had a lower frequency of severe complications, thus the efficacy of RFA was thought to be equal to a surgical procedure.

Ultrasonography screening for hepatocellular carcinoma in Japanese patients with diabetes mellitus.

BACKGROUND: Effective surveillance for hepatocellular carcinoma (HCC) in diabetes mellitus (DM) has not been established. We elucidated the risk factors for HCC in DM patients. METHODS: From 2000 to 2014, 80 patients diagnosed with HCC for the first time who had concomittant DM but no other etiology of liver disease were enrolled as the DM-HCC group. From 2005 October to 2014, after introduction of the abdominal ultrasonography (US) report database, 2083 DM patients with no viral hepatitis, no known autoimmune hepatic diseases, and/or no evidence of alcohol abuse (>60 g/day) were enrolled as the DM-US group. Findings from the first US screening were evaluated. "Elderly" patients were defined as those aged >65 years. Clinical features of DM-HCC patients were evaluated and compared with those of DM-US patients. RESULTS: In the DM-HCC group (54 men, 26 women), the mean (± SD age was 74.1 ± 8.5 years, and mean HbA1c and fibrosis-4 (FIB-4) index were 7.3 ± 1.3% and 4.50 ± 3.42, respectively. Mean tumor diameter was 5.7 ± 3.5 cm, there were 63/13/2/2 patients classified as Child-Pugh A/B/C/unknown, and 56/24 were single/multiple lesions. In the DM-US group, HCC was detected in three patients (0.14%; 0.3% of those classified as elderly). The mean age and FIB-4 index of these three patients (one man, two women) were 75.6 years (range 67-92 years) and 4.84 (range 2.87-6.98), respectively. Mean tumor diamter was 7.6 cm and there were one and two single and multiple lesions, respectively. In elderly DM-US patients with a high FIB-4 index (≥4), the rate of HCC detection was 5.0%. CONCLUSIONS: Being elderly and having a high FIB-4 index are characteristic features of DM-HCC. Similar characteristics were noted for patients with HCC in the DM-US group. HCC surveillance with US is recommended for DM patients, especially those who are elderly (≥65 years) and have a high FIB-4 index.

Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: computed tomography is useful for evaluation.

BACKGROUND/AIM: The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings. METHODS: We enrolled 988 CLD (736 with naïve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm(2))/height (m)(2)] was calculated using personal computer software. The cut-off level for pre-sarcopenia was defined as less than two standard deviations (SDs) below the mean PI value in the NCs under 55 years old [males, 45.6 ± 5.7 years (n = 61), 4.24 cm(2)/m(2); females, 47.0 ± 6.1 years (n = 49), 2.50 cm(2)/m(2)]. Elderly was defined as 65 years or older. Clinical features were retrospectively evaluated. RESULTS: In the CLD group (HCV:HBV:HBV and HCV:alcohol:non-HBV and HCV = 652:88:7:82:159), pre-sarcopenia was observed in 15.3% of patients with chronic hepatitis (CH), 24.4% of those with liver cirrhosis (LC) Child-Pugh A, 37.7% of those with LC Child-Pugh B, and 37.1% of those with LC Child-Pugh C. A comparison between NC and CH by age (<55, 55-64, 65-74, ≥75 years) showed that the frequency of pre-sarcopenia was higher in CH regardless of age (1.8 vs. 3.6%, 3.2 vs. 15.9%, 4.9 vs. 13.4%, 14.3 vs. 20.2%, respectively). PI values showed correlations with BMI (r = 0.361), age (r = -0.167), albumin (r = 0.115), and branched-chain amino acids (r = 0.199) (P < 0.01). CONCLUSION: Retrospective evaluate for pre-sarcopenia was easy to perform with CT findings. Nutrition and exercise instruction should be considered for early stage and even non-elderly CLD as well as LC.

Prognosis and therapy for ruptured hepatocellular carcinoma: problems with staging and treatment strategy.

BACKGROUND: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices. MATERIALS/METHODS: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV+HCV 1, alcohol 2, others 15; naïve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis. RESULTS: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C=14:15:5 vs. 4:9:20, P<0.001) was better, while the percentage of patients with multiple tumors was lower [19/34 (55.9%) vs. 29/33 (87.9%), respectively; P<0.001] in the naïve group. The 1- and 3-year survival rates were better in the naïve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P<0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P=0.010). CONCLUSION: In patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis, better prognosis can be expected with curative treatment. The present naïve group included more of such cases than the recurrent group, indicating the effectiveness of curative therapy.

Colonic intussusception caused by anisakiasis: a case report and review of the literature.

A 67-year-old woman presented with periumbilical pain. Contrast-enhanced computed tomography findings indicated intussusception of the ascending colon without ischemia or necrosis, and we performed successful colonoscopy to treat the condition. Furthermore, an edematous area caused by anisakis was detected in the ascending colon and the anisakis was removed. The patient noted that she had eaten raw fish one day before the symptoms developed. Although colonic intussusception caused by anisakiasis is extremely rare, colonoscopy should be performed in colonic intussusception patients suspected of having anisakiasis in order to avoid invasive resection.

An adult patient with acute infection with hepatitis B virus genotype C that progressed to chronic infection.

In 2008, a 28-year-old woman consulted our hospital due to general fatigue. Her ALT level was within normal range but she was positive for hepatitis B surface antigen (HBsAg). Her ALT level was nearly within normal range thereafter and she was consistently positive for HBeAg. Later, it was proven that she was negative for HBsAg in 1999. She had been a sex worker in 2007-2008. Complete genome sequencing revealed that her HBV was genotype C. The present case may indicate that it is possible for acute infection with HBV genotype C to progress to chronic infection in adults.

Huge pancreatic acinar cell carcinoma with high levels of AFP and fucosylated AFP (AFP-L3).

A 25-year-old Japanese woman with a large abdominal tumor (10 cm in diameter) and high level of serum alpha-fetoprotein (AFP, 1,222.4 ng/mL) was introduced and admitted to our hospital in January 2011. Pre-operative imaging modalities could not identify the tumor origin. There was no chronic hepatic viral disease, however, the elevated level of fucosylated AFP (87.8%) and connection with the left hepatic lobe led us to diagnose the tumor as a hepatocellular carcinoma. Surgical resection was performed in February. Histological findings revealed a pancreatic acinar cell carcinoma (ACC). Herein, we provide details of this difficulty to diagnose a case of ACC.

Hepatocellular carcinoma in a case of Wilson's disease treated with radiofrequency ablation therapy.

A 37-year-old Japanese man was diagnosed with liver cirrhosis due to Wilson's disease in 2001 and treated with D-penicillamine. Thereafter, he was admitted to our hospital for further examination of a space occupying lesion in the liver. The patient was diagnosed with hepatocellular carcinoma (HCC) (7th segment, 2.5 cm in diameter) in May 2010 and treated with radiofrequency ablation therapy. Biopsy findings from a non-cancerous area revealed a fatty liver, though cirrhotic nodules were not found. Long-term treatment for Wilson's disease may improve hepatic fibrosis, and careful screening for HCC by abdominal imaging is needed in such cases.

Severe hypoglycemia associated with insulin-like growth factor II-producing liver metastasis from gastric carcinoma treated with overnight total parenteral nutrition via a central vein catheter reserve port.

Hypoglycemia caused by insulin-like growth factor II is difficult to control. A 77-year-old woman was diagnosed with gastric cancer and multiple liver metastases in September 2006 and underwent chemotherapy; however, at that time there were no symptoms of hypoglycemia. From January 2007 onwards, hypoglycemic comas and symptoms of hypoglycemia began to appear frequently. Her serum level of insulin was normal; thus, we suspected the presence of big insulin-like growth factor II was causing the hypoglycemia. This was proven by Western immunoblotting and we diagnosed non-islet cell tumor hypoglycemia associated with gastric cancer. Overnight nutrition provided via a central venous catheter port to prevent hypoglycemia allowed the patient to become ambulant and to remain free of hypoglycemic coma at follow-up until her death 7 months later.

Clinical translation in the treatment of hepatocellular carcinoma following the introduction of contrast-enhanced ultrasonography with Sonazoid.

Some hepatocellular carcinoma (HCC) nodules are detectable with dynamic computed tomography, but not by conventional B-mode ultrasonography (US). Contrast-enhanced US (CEUS) with Sonazoid, a new injectable contrast agent, has been used in Japan since January 2007. The primary advantage of this agent is the ability to maintain observations continuously in the Kupffer phase. We assessed the clinical role of CEUS with Sonazoid for radiofrequency ablation (RFA). From January 2005 to December 2008, 1142 patients were treated with surgical resection, RFA, percutaneous ethanol injection or transcatheter arterial chemoembolization, following the exclusion of those patients treated with chemotherapy or supportive care. The patients included in the study were divided into the pre-CEUS (n=451, 2005 and 2006) and post-CEUS (n=691, 2007 and 2008) groups. Clinical background (e.g., etiology, Child-Pugh classification, tumor node metastasis stage, percentage of patients matched with Milan criteria and selected therapies) was compared between the two groups. In addition, naïve cases were compared between the groups. There were 130 naïve HCC cases in the pre-CEUS group and 171 in the post-CEUS group. Although there were no significant differences for clinical background, the percentage of RFA cases increased from 21 (n=95) to 32% (n=219) and from 32 (n=41) to 52% (n=89) for total and naïve subjects, respectively, after CEUS was introduced (P<0.01). In naïve cases treated with RFA, tumor numbers in the post-CEUS group were larger than those of the pre-CEUS group (1.15±0.48 vs. 1.40±0.67; P<0.01). CEUS with Sonazoid, therefore, makes it possible to perform RFA in a considerable number of HCC cases that would otherwise be invisible by conventional B-mode US.

Modified technique for determining therapeutic response to radiofrequency ablation therapy for hepatocellular carcinoma using US-volume system.

In radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), microbubbles appearing during the procedure make it difficult to determine effectiveness with ultrasonography (US) imaging. We developed a modified US-volume system and evaluated its efficacy for demonstrating response to therapeutic RFA. Our US-volume system displays multiplanar reconstruction (MPR) images providing a synchronized view with a US image along with past US-volume data in real-time side-by-side on a personal computer. Seventy-eight patients (94 nodules) were enrolled, of whom 35 (47 nodules) were evaluated using this system (US-volume group) and compared to the other 43 (47 nodules) examined before development of our system (control group). All nodules were clearly depicted by US. If the shortage of margin was predicted with US-volume system, we performed additional needle insertion. Tumor necrosis following RFA was graded by dynamic computed tomography as follows: Grade A, necrotic area surrounded in all directions with an adequate margin (>or=5 mm); Grade B, necrotic area surrounded in all directions, though some margin areas <5 mm; and Grade C, residual tumor or necrotic area smaller than the target tumor. In the US-volume group, the average tumor size was not smaller than that in the control (15.9+/-4.9 vs. 16.0+/-4.3 mm) and adequate margins were obtained (Grade A, B, C, 45/1/1 vs. 35/8/4; P<0.01). Further, there was a significant reduction in numbers of RFA sessions as compared to the control (1.03+/-0.17 vs. 1.12+/-0.32; P<0.01). In HCC patients undergoing RFA, our modified US-volume system accurately demonstrated therapeutic response, which led to a reduced number of RFA sessions.

Malignant pheochromocytoma with liver metastasis treated by transcatheter arterial chemo-embolization (TACE).

Multiple liver metastatic lesions were shown by computed tomography and scintigraphy with 123I- metaiodobenzylguanidine (MIBG) in a 76-year-old woman 2 years after resection of a pheochromocytoma of the right adrenal gland. Transcatheter arterial chemo-embolization (TACE) was performed for the liver metastasis, with blood pressure strictly controlled by administration of doxazosin and phentolamine for the prevention of hypertensive crisis after TACE. There were no severe adverse events associated with the treatment, and the number and size of the lesions were decreased. TACE with strict blood pressure control was an effective and safe therapy for multiple liver metastatic lesions related to malignant pheochromocytoma.

Amino acid imbalance in patients with chronic liver diseases.

AIM: The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS: We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. RESULTS: The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower (P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher (P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 +/- 103 in F1, 483 +/- 122 in F2, 487 +/- 111 in F3 and 423 +/- 94 in F4). CONCLUSION: A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage.