Ten-year long-term results after non-surgical management of hepatolithiasis, including cases with choledochoenterostomy.

BACKGROUND: Long-term follow-up of non-surgical procedures for the management of hepatolithiasis has been reported, but risk factors for mortality have not been properly evaluated. METHODS: We conducted a retrospective study of the case records of 121 patients with hepatolithiasis who underwent endoscopic retrograde cholangiopancreatography (ERCP), peroral cholangioscopy (POCS), percutaneous transhepatic cholangioscopy (PTCS), or conservative treatment at the Department of Gastroenterology of Chiba University Hospital between January 1980 and July 2011. The primary outcome measure was mortality, defined as death due to hepatolithiasis (concomitant liver failure with cholangitis and cholangiocarcinoma). RESULTS: Complete clearance of intrahepatic stones was achieved in 22 (57.8%) of 38 patients by POCS, in 12 (66.7%) of 18 patients by ERCP, and in 10 (52.6%) of 18 patients by PTCS. The remaining 46 patients were treated conservatively. The mean follow-up period was 11.4 ± 7.1 years (range, 0.6-32.8). There were 14 hepatolithiasis-related deaths (11 with cholangiocarcinoma and three from liver failure with cholangitis) during the follow-up periods. Multivariate Cox proportional hazards analysis revealed liver atrophy (P = 0.015; HR = 3.98; 95% CI, 1.30-12.20) and congenital biliary dilatation after biliary-enteric anastomosis (P = 0.036; HR = 4.57; 95% CI, 1.11-18.87) as significant risk factors for mortality. CONCLUSIONS: Analysis of the 10-year long-term results after non-surgical management of hepatolithiasis identified liver atrophy and congenital biliary dilatation as risk factors for mortality. Patients with hepatic lobe atrophy should undergo a hepatectomy, if operable.

Inflammation in background cirrhosis evokes malignant progression in HCC development from HCV-associated liver cirrhosis.

OBJECTIVE: It is accepted that inflammation promotes malignant progression in the development of cancers. Whether, this is true for hepatocellular carcinoma (HCC) remains as an open question. We examined the relationship between the inflammatory histology activity index (HAI) in the background liver cirrhosis (LC) and the histological grading of the HCC in the hepatectomized HCC patients with HCV-associated LC. MATERIAL AND METHODS: Out of 264 HCC patients who underwent curative hepatic resection, 197 had HCV-associated LC. Among them, 52 patients with a small solitary HCC nodule (< 5 cm in diameter) were studied. Inflammation in the background LC was evaluated by modified Knodell's HAI. To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (0-4, each) were estimated. The average HAI was calculated. The grade of malignancy of HCC was determined by WHO classification. RESULTS: The average HAI in the 15 patients with moderately differentiated HCC (4.3 ± 0.8, mean ± SD) was significantly larger than that in 11 patients with well differentiated HCC (3.5 ± 0.6, p = 0.036). The HAI in the 24 patients whose HCC nodules contained poorly differentiated HCC (5.2 ± 1.1) was significantly larger than that in patients with moderately differentiated HCC (p = 0.025). Thus, the HAI order was well differentiated group < moderately differentiated group < poorly differentiated group. CONCLUSIONS: Inflammation in the background non-cancerous cirrhotic portion would evoke malignant progression in HCC development from HCV-associated LC.

Severe inflammation in the background liver cirrhosis correlates with the development of poorly differentiated HCC in HCV-associated liver cirrhosis.

OBJECTIVE: Whether severe inflammation in the background liver cirrhosis might correlate with the development of poorly differentiated human hepatocellular carcinoma (HCC) was studied in hepatitis C virus (HCV)-associated liver cirrhosis. METHODS: Out of 214 HCC patients who underwent curative hepatic resection, 148 patients were HCV-associated liver cirrhosis (LC) patients. Out of these 148, 31 patients with small solitary HCC nodule (diameter ≤ 3 cm) were included in this study. Inflammation in the background LC was evaluated by modified histology activity index (HAI). To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (each 0-4) were estimated. In each case, the average HAI was calculated. The grade of malignancy of HCC was determined by World Health Organization (WHO) classification. RESULTS: The average HAI score in the cirrhotic portion in 17 patients with poorly differentiated HCC (5.21 ± 1.15, mean ± standard deviation (SD)) was significantly larger than that in 14 patients without poorly differentiated HCC (4.05 ± 0.83, p<0.005). The occurrence rate of HCC containing poorly differentiated HCC component in the patients whose HAI was more than 5.0 was 80.0% (12 out of 15), and was significantly higher compared with those in patients whose HAI was less than 5.0 (5 out of 16, 31.3%, p<0.025). In univariate and multivariate analyses for contribution to poorly differentiated HCC development, HAI was the only significant contributor (p=0.011, p=0.012 respectively). CONCLUSION: It is suggested that severe inflammation in the background cirrhosis accelerates the promotion in the HCC development from HCV-associated LC.

[Retroperitoneal metastasis of hepatocellular carcinoma - a case report].

The patient was a 54-year-old man. He was an HBV carrier, and hepatocellular carcinoma (HCC) was detected for the first time in 2000. An operation was performed, but HCC recurred. After repeating the operation and transarterial chemo-embolization (TACE) for the recurrent HCC, a tumor was found in January 2009 on the ventral side of the right kidney, and we thought it was a retroperitoneal metastasis of HCC or peritoneal dissemination. He was enrolled in a trial of systemic chemotherapy, called "S-1 monotherapy for extrahepatic metastasis of HCC", but the tumor seemed progressive. Since he showed no other lesion, he was indicated for surgical resection. Intraoperatively, the tumor was localized between the duodenum and the right kidney, and was covered by the retroperitoneum. Pathological examination of the resected specimen revealed retroperitoneal metastasis of HCC. Intrahepatic recurrence was detected 6 months after the resection. Therefore, he underwent TACE, and he is currently (1 year after surgery) alive without any extrahepatic metastasis. We describe herein this case because retroperitoneal metastasis of HCC is very rare.

[Case of intrahepatic cholangiocarcinoma drained through a fistula of the duodenal bulb].

A 72-year-old woman presented with epigastric discomfort. A low density tumor was found in the hilum and left liver by CT. Since she complained epigastralgia, upper gastrointestinal endoscopy was performed, showing an ulcer in the duodenal bulb, with poorly-differentiated adenocarcinoma seen on a biopsy specimen from the edge of the ulcer. After admission, poorly-differentiated adenocarcinoma cells were also obtained with ultrasound guided aspiration cytology of the liver tumor. We diagnosed intrahepatic cholangiocarcinoma (IHC), and treated with gemcitabine. During chemotherapy, the duodenal ulcer became a fistula, and the liver tumor diminished with bubbles inside it. It was suggested that liquid material of IHC, such as necrotic tissue and mucin, drained to the duodenal bulb during chemotherapy.

Usefulness of peroral cholangioscopy in preoperative diagnosis of intraductal papillary neoplasm of the bile duct.

Surgical resection is considered the first-line treatment of intraductal papillary neoplasm of the bile duct (IPNB). Since some patients with IPNB have an unexpectedly superficially-spreading lesion, preoperative cholangioscopic diagnosis is very useful in determining the extent of resection. We report a patient with IPNB in whom preoperative peroral cholangioscopic evaluation was useful.

Long-term outcome of endoscopic papillotomy for choledocholithiasis with cholecystolithiasis.

AIM: To assess long-term outcome of endoscopic papillotomy alone without subsequent cholecystectomy in patients with choledocholithiasis and cholecystolithiasis. METHODS: Retrospective review of clinical records of patients treated for choledocholithiasis and cholecystolithiasis from 1976 to 2006. Of 564 patients subjected to endoscopic papillotomy and endoscopic stone extraction, 522 patients (279 men, 243 women; mean age 66.2 years) were followed up and predisposing risk factors for late complications were analyzed. RESULTS: The mean duration of follow up was 5.6 years. Cholecystitis and recurrent choledocholithiasis occurred in 39 (7.5%) and 60 (11.5%) patients, respectively. Cholecystitis, including one severe case, resolved with conservative treatment. Recurrent choledocholithiasis was successfully treated endoscopically except in one case. Pneumobilia was found to be a significant risk factor for cholecystitis (P = 0.019) and recurrent choledocholithiasis (P = 0.013). Biliary tract cancer occurred in 16 patients; gallbladder cancer in 13 and bile duct cancer in three. Gallbladder cancer developed within 2 years after endoscopic papillotomy in seven of the 13 patients (53.8%). CONCLUSION: Pneumobilia was the only significant risk factor for cholecystitis and recurrent choledocholithiasis in our study population. As for the long-term outcome, it was unclear whether endoscopic papillotomy contributed to the occurrence of biliary tract cancer.

Endoscopic diagnosis of intraductal papillary mucinous neoplasm of the bile duct.

BACKGROUND/PURPOSE: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is considered an uncommon tumor. The purpose of this study was to evaluate the diagnostic utility of endoscopic cholangiography (ERC) with subsequent peroral cholangioscopy (POCS) and/or intraductal ultrasonography (IDUS) for this tumor. METHODS: From December 1991 to November 2006, a retrospective analysis was made of eight patients with IPMN-B. Their clinical features and the endoscopic diagnostic strategy for POCS and IDUS were reviewed. RESULTS: In all the patients, ERC failed to show papillary tumors, due to coexisting mucin or biliary sludge. POCS was carried out after ERC and it showed the presence and locations of papillary tumors in all patients, except for one with a tumor in the peripheral intrahepatic bile duct (B3). IDUS was performed in seven of the eight patients; in five of these patients, intraductal protruding tumors were clearly visualized, whereas flat tumors were not identified in the remaining two patients. In one of the eight patients, endoscopic nasobiliary drainage did not remove the huge amount of mucin. Hence, this patient required subsequent percutaneous biliary drainage. Six of the eight patients underwent surgical treatment; five patients underwent a hepatic resection with or without extrahepatic bile duct resection and one underwent a pancreaticoduodenectomy. Five of the six operated patients are still alive; one patient died of gastric cancer 90 months after the operation (mean follow-up period, 45.3 months). The two remaining patients, who were considered inoperable due to major medical comorbidities, died of liver failure and cholangitis 3 and 6 months, respectively, after stent placement. CONCLUSION: ERC failed to delineate intraductal papillary tumors, due to coexisting mucin. The presence and location of papillary tumors were correctly diagnosed by both POCS and IDUS, but POCS may be better than IDUS to diagnose the extent of the tumor.

The successful use of peroral cholangioscopy for the diagnosis and treatment of the biliary tract lesions and giant bile duct stones in a 76-year-old man.

We encountered a case in whom peroral cholangioscopy was useful for the diagnosis and treatment of irregular biliary tract mucosa and giant bile duct stones. Peroral cholangioscopy seems to improve the diagnosis of biliary tract diseases and allow internal treatment. The proper diagnosis of biliary tract diseases may be further confirmed by the concomitant use of narrow band imaging and this endoscopic technology.

High serum alanine aminotransferase levels for the first three successive years can predict very high incidence of hepatocellular carcinoma in patients with Child Stage A HCV-associated liver cirrhosis.

Abstract Objective. To assess retrospectively whether continuously high serum alanine aminotransferase (ALAT) levels (<80 IU) in the first three successive years after the diagnosis of liver cirrhosis (LC) are predictive of a subsequent high incidence of hepatocellular carcinoma (HCC) in patients with Child Stage A hepatitis C virus (HCV)-LC. Material and methods. The study comprised 132 HCV-LC (Child Stage A) patients who had not received interferon therapy but had been treated with anti-inflammatory agents. At the end of a 3-year follow-up after the diagnosis of LC, the patients were subdivided into three groups according to their serum ALAT levels and the subsequent incidence of HCC was assessed. Results. The cumulative incidence of HCC starting from 3 years after the diagnosis of LC in the continuously high ALAT group (annual average over 3 years always > or =80 IU; n=41; Group A) was markedly higher than that in the continuously low ALAT group (always <80 IU; n=48; Group B) (p<0.005) during an observation period of 7.9+/-3.7 years. The incidence of HCC in Group A was 11.8%/year. The odds ratios of developing HCC in Group A and Group C (mixed high and low ALAT levels; n=43) were 5.1-fold and 1.5-fold that of Group B, respectively. A multivariate analysis revealed that the ALAT group was independently associated with HCC development. Conclusions. Continuously high ALAT levels for three successive years following the diagnosis of LC can be predictive of a very high incidence of HCC in Child A HCV-LC patients. Prospective trials using therapeutic approaches aimed at decreasing ALAT levels are necessary in order to confirm a positive impact of ALAT reduction on the incidence of HCC in patients with HCV-LC.

The usefulness of perfusion-weighted magnetic resonance imaging in advanced pancreatic cancer.

OBJECTIVES: Perfusion-weighted magnetic resonance imaging (MRI) can detect the changes of signal intensity in tumors. We evaluated the prognostic value of perfusion-weighted MRI in patients with advanced pancreatic cancer (PC). METHODS: Perfusion-weighted MRI was performed before treatment on 27 consecutive patients with advanced PC. The American Joint Committee on Cancer (AJCC) stages of patients were as follows (8, stage III; 19, stage IV). Imaging acquisition was continually repeated with echo planar sequence every 2 seconds for 2 minutes after a bolus injection of gadolinium. We made a time intensity curve of PC and calculated the signal ratio (SR) on perfusion-weighted imaging. We assessed the relation between SR and clinical factors including tumor stage, lymph node metastasis, liver metastasis, and so on. Patients were divided into low and high SR group and compared SR with the overall survival. RESULTS: All cases showed transient decreases signal intensity (SR, 6.9-55.7%). These patients were classified into 2 groups at cutoff median SR of 22.0% The high SR group significantly correlated with the higher stage (P=0.03) and the presence of lymph node metastasis (P=0.04). The high SR group had significantly shorter overall survival (P=0.04). CONCLUSIONS: Perfusion-weighted MRI may predict the survival in advanced PC patients.

Clinical evaluation of endosonography-guided biliary drainage for patients with the difficulty with placing of internal drainage.

The methods for non-surgical biliary drainage for the treatment of obstructive jaundice generally include transpapillary one, or endoscopic retrograde cholangiopancreatography (ERCP), and percutaneous one, or percutaneous transhepatic biliary drainage (PTBD). In placing internal drainage, a stent is frequently inserted through the route of the drainage. However, transpapillary approach may be infeasible in patients, if cannulation is difficult, drainage cannot reach the duodenal papilla, and percutaneous approach may be infeasible in patients, if the intrahepatic bile duct is not be expanded. Endosonography-guided biliary drainage (ESBD) is a new method enabling internal drainage of an obstructed bile duct. In this study, the transpapillary ESBD approach was successfully applied to a patient having obstructive jaundice due to cancer of the head of the pancreas during the treatment of ovarian cancer although internal drainage via transpapillary and percutaneous approach was not applicable to this patient. So far, few studies have reported the use of ESBD. Although a large-scale, multicenter study is required to investigate the indications and complications of ESBD, it is no doubt that we have now more treatment options for non-surgical biliary drainage.

Clinical utility of peroral cholangioscopy for mucin-producing bile duct tumor.

BACKGROUND/AIMS: The purpose of this study was to examine the clinical utility of peroral cholangioscopy for mucin-producing bile duct tumor. METHODOLOGY: Peroral cholangioscopy was performed in seven cases of mucin-producing bile duct tumor to decide the course of treatment based on the results. All seven cases were evaluated by peroral cholangioscopy and examined by a transpapillary biopsy. Five out of the seven cases (71.4%) were adequately observed. Because abundant mucin could not be removed in 2 cases (28.6%), one of them underwent PTCS after PTBD, and the other had surgery for EBD insertion without PTBD at the patient's request. A stent was placed by surgery in five out of the seven cases and by a transpapillary method in two cases. RESULTS: Among the five cases that could be evaluated by peroral cholangioscopy, the excised specimens were compared with the findings obtained from peroral cholangioscopy in three cases that underwent surgery, while the results of transpapillary mapping biopsy were compared with the findings obtained from peroral cholangioscopy in two inoperable cases, showing that the evaluation by peroral cholangioscopy agreed with the results of tumor staging in all the five cases. CONCLUSIONS: This study suggested the possibility that the use of peroral cholangioscopy for mucin-producing bile duct tumor could be useful in deciding the course of treatment.

[A resected case of metastatic pancreatic cancer from cecal carcinoma].

A 64-year-old woman underwent an ileocecectomy in July 2002 for ruptured cecal carcinoma, which was a well-differentiated adenocarcinoma, stage II, ss, ly0, v0, n (-). In August 2005, abdominal CT revealed a tumor 20mm in diameter in the pancreatic tail, therefore, a distal pancreatectomy and splenectomy were performed. The pancreatic tumor resembled the moderately differentiated cecal adenocarcinoma, both having p53 and k-ras point mutations in common, and it was diagnosed as a metastasis of the cecal carcinoma.

Value of peroral cholangioscopy for mucin-producing bile duct tumor.

Mucin-producing bile duct tumor is a rare biliary tract tumor. Despite the development of modern diagnostic technologies such as ultrasonography, and angiography, the precise determination of this tumor is difficult because of ambiguity caused by the abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Given these problems, selective percutaneous transhepatic biliary drainage (PTBD) and percutaneous transhepatic cholangioscopy (PTCS) are indispensable for the accuracy staging of this cancer. But, PTCS has a risk of a rare but serous complications, seeding metastasis at the sinus tract of PTBD, whereas the retrograde approach minimizes this risk. We report the case of a patient who underwent the successful resection of a mucin-producing bile duct tumor. The tumor was diagnosed preoperatively as originating in the left caudate lobe after ERC and peroral cholangioscopy (POCS).

Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma.

BACKGROUND: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. METHODS: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. RESULTS: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. CONCLUSIONS: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.

Diagnostic value of MRCP and indications for ERCP.

BACKGROUND/AIMS: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) and examine the indications for endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: MRCP was performed in 185 patients with hepatobiliary disease in whom abdominal ultrasonography (US) had not been of diagnostic value. These patients were selected for MRCP in view of their abdominal symptoms, high levels of hepatobiliary enzymes, and pancreatic/bile duct dilatation found by abdominal US. Based on MRCP findings, 75 patients were selected for ERCP. RESULTS: ERCP provided new findings in 14 (18.%) patients. In 110 patients subjected to only MRCP and follow-up as well as in 75 patients with MRCP followed by ERCP, MRCP-based diagnosis corresponded with the final diagnosis. In our study, patients who would have conventionally required ERCP, such as those with natural passed choledocholithiasis and postoperative bile duct dilatation, could be followed up without ERCP. These results the importance of considering indications for ERCP. CONCLUSIONS: MRCP can be an alternative to ERCP at least for diagnosis.

Reduction therapy of alanine aminotransferase levels prevent HCC development in patients with HCV-associated cirrhosis.

BACKGROUND: To find a way to prevent the development of hepatocellular carcinoma (HCC) from hepatitis C virus-associated liver cirrhosis (HCV-LC), an analysis of the HCV-LC patients who had received reduction therapy of the alanine aminotransferase (ALT) levels was performed. PATIENTS AND METHODS: Seventy-four consecutive HCV-LC patients of Child Stage A were followed for >10 years for the development of HCC. They were divided into two groups: in group A, the reduction therapy for the ALT levels was aggressively performed, while in group B, the reduction therapy was not performed aggressively. The patients were subdivided into three sub-groups according to their serum ALT levels. In groups A and B, the high ALT group was comprised, respectively, of nine and five patients whose annual average serum ALT levels were persistently high (> or =80 IU), while the low ALT group was comprised of 19 and 20 patients whose annual average serum ALT levels were persistently low (<80 IU). The remaining eleven and ten patients had annual average serum ALT levels which fluctuated and were unclassified (unclassified group). RESULTS: In group B, 65.7% of the patients had developed HCC in 13 years, in contrast to only 41.0% of group A (p=0.039). In group A, the median HCC development time was 12.8 years, in contrast to only 3.8 years in group B (p=0.0013). Multivariate analysis demonstrated that the mode of reduction therapy and ALT levels were the significant factors affecting HCC development. CONCLUSION: The chances of surviving for more than ten years without developing HCC for HCV-LC patients

[Evaluation of biliary stenting therapy for malignant biliary stricture at our hospital].

The clinical results of biliary stenting therapy for non-resectable malignant biliary stricture were assessed for patency periods and survival periods in consideration of the types of stents and disease. The subjects were 51 patients with non-resectable malignant biliary stricture due to disease of the pancreas and biliary tract treated at our hospital between April 2001 and March 2005. No significant differences were observed in the patency periods and survival periods among the various types of stents. In regard to the type of disease, the survival period for biliary tract cancer was longer (616 +/- 246 days) than those for other diseases. There was no difference in the number of times of stenting among the various stents, and jaundice was effectively reduced. No patients in our series died of failure to reduce jaundice. We therefore considered it necessary to choose a proper stent indwelling route and a stent type according to stricture site, disease type and PS (performance status) at the time of stenting. The usefulness of the biliary stenting therapy for non-resectable malignant biliary stricture was suggested.

Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis.

In a previous study of patients with hepatitis C virus (HCV)-associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean +/- SD dosage of UDCA administered in group A was 473.7 +/- 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 +/- 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.