Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization.

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.

A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients.

BACKGROUND: Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. METHODS: Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m(-2). The primary end point was disease-control rate (DCR). RESULTS: Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. CONCLUSIONS: ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.

Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan.

BACKGROUND: The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. AIM: To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. CONCLUSION: A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients.

Nuclear HBcAg and histology activity index as independent predictors of the expression of singly spliced HBV-RNA.

Although hepatitis B virus (HBV) RNA splicing has been reported by many researchers, the clinical significance of this event remains illusive. The present study was designed to investigate the clinical roles of singly spliced HBV-RNA. Liver biopsy tissues obtained from 32 consecutive patients were subjected to reverse transcriptase-polymerase chain reaction for the detection of singly spliced and unspliced HBV-RNA. Stepwise linear regression model was used to estimate the ratio of singly spliced to unspliced (S/US) HBV-RNA in the presence of the following variables: age, gender, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alpha-foetoprotein, status of HBV e antigen (HBeAg), status of antibody to HBeAg, HBV-DNA, histology activity index (HAI), fibrotic score, grade of cytoplasmic HBV core antigen (HBcAg), grade of nuclear HBcAg, genotype, status of precore-stop-mutation, basal core promoter mutation, previous lamivudine therapy and superinfection by other hepatitis viruses. The results showed that HAI (beta = -0.2616; P = 0.011) and grade of nuclear HBcAg expression (beta = 0.5599; P =0.0067) were two independent predictors for the expression of singly spliced HBV-RNA. Further categorical analysis showed that patients with HAI score or=2 have significantly higher S/US ratios. In conclusion, nuclear HBcAg and HAI are two independent predictors for the expression of singly spliced HBV-RNA.

Comparison of long-term effects of lymphoblastoid interferon alpha and recombinant interferon alpha-2a therapy in patients with chronic hepatitis B.

To compare the long-term effect of natural lymphoblastoid interferon-alpha (IFN-alpha nl) and recombinant IFN-alpha 2a therapy in patients with chronic hepatitis B, 210 patients in two trials were followed-up for 1.1-15.5 years following the end of therapy. They included 34 patients who received placebo (control), 67 treated with IFN-alpha nl (36 after prednisolone priming) and 109 treated with IFN-alpha 2a (56 after prednisolone priming). The cumulative sustained response was higher in patients who had been treated with IFN-alpha nl after prednisolone priming than was exhibited using IFN-alpha nl alone, IFN-alpha 2a alone or the placebo (P < 0.05), or IFN-alpha 2a following prednisolone priming (P = 0.052) at the end of 11 years. Hepatocellular carcinoma (HCC) was detected in 1.5% of the IFN-alpha nl group, 3.7% of the IFN-alpha 2a group and 14.7% of the control group (control vs IFN-alpha nl or IFN-alpha 2a, P < 0.05). The cumulative HCC development was higher in the control group than in the IFN-alpha nl group (P < 0.002) and the IFN-alpha 2a group (P = 0.06). The cumulative survival rate was lower in the control group than in the IFN-alpha nl group (P < 0.01) and the IFN-alpha 2a group (P = 0.02). Multivariate analysis revealed that IFN-alpha nl therapy and female gender are significant predictors of sustained response; preexisting cirrhosis, age at entry and IFN therapy are significant factors in both HCC development and survival. In conclusion, IFN-alpha nl treatment may have a better long-term effect on hepatitis B virus (HBV) clearance than IFN-alpha 2a and placebo, and IFN therapy may provide better long-term beneficial effects than placebo in terms of HBV clearance, reduction of HCC and prolonged survival.

Sequential changes of hepatitis C virus antibody profiles during treatment of chronic hepatitis C of genotype 1b: pretreatment antibody response to E2/NS1 correlated sustained response.

BACKGROUND: This study aimed to investigate the relation between hepatitis C virus (HCV) antibody profiles and response to therapy of chronic HCV infection of genotype 1b. MATERIALS AND METHODS: Quantitative assays of antibody response to HCV antigens were performed sequentially using immunoblot confirmatory assays in 25 patients with genotype 1b chronic hepatitis C who received a 24-week course of interferon and ribavirin therapy. RESULTS: 12 patients had a sustained response (group A), and 13 did not (group B). Serum titers of HCV RNA were significantly higher in group B than in group A (p = 0.02). Pretreatment antibody reactivity to core, NS3, NS4, and NS5 antigens did not differ significantly between the two groups, but group A had significantly higher titers of anti-E2/NS1 than group B (p = 0.04). Sustained response was noted in none of seven patients with HCV RNA > 10(6) copies/ml, but did occur in 12 of 18 patients with HCV RNA < 10(6) copies/ml (p < 0.01). Among the latter, all seven patients with anti- E2/NS1 had sustained responses, as did five (45%) of 11 without (p = 0.04). Antibody profiles changed little or not at all at the end of treatment or at 6 months after treatment in both groups. CONCLUSION: In chronic hepatitis C of genotype 1b, patients with HCV RNA > 10(6) copies/ml respond poorly to therapy compared to those with HCV RNA < 10(6) copies/ml. Among the latter, the presence of pretreatment anti-E2/NS1 correlated with sustained response. Quantitative assay of antibody response to HCV antigens at the end of treatment had no additional value to predict a sustained response.

Unintentional rechallenge resulting in a causative relationship between ketoconazole and acute liver injury.

We present the case of a female patient in whom acute overt hepatitis developed after 60 days of ketoconazole administration (200 mg/day). A prompt renewed hepatic injury 48 hours after an unintentional rechallenge 30 months later provided definitive evidence for a causative relationship between ketoconazole and acute liver injury. Histological examination revealed acute hepatitis with bridging hepatic necrosis. Clinicians should be aware of this cause and effect relationship between ketoconazole and acute liver injury, which can result in prompt severe acute liver injury after rechallenge.

Long-term results of endoscopic hemorrhoidal ligation: two different devices with similar results.

BACKGROUND AND STUDY AIMS: To evaluate the efficacy of two different endoscopic hemorrhoidal ligation (EHL) devices for symptomatic internal hemorrhoid. PATIENTS AND METHODS: From November 2000 to February 2001, 218 consecutive patients with symptomatic internal hemorrhoids were enrolled. A total of 109 patients were treated with an EHL device 9 mm in diameter (group A); the rest were treated with a device 13 mm in diameter (group B). The patients' clinical presentations were rectal bleeding and prolapse. The severity of the hemorrhoid was classified using Goligher's grading. RESULTS: All patients were treated for one session, and were followed from 19 to 24 months (mean 22.4 months). The number of band ligations averaged 2.59 in group A and 1.68 in group B. Most patients had their hemorrhoids reduced by at least one grade (82.8 % in group A and 90.8 % in group B). Rectal bleeding was controlled in 108 patients (99.1 %) in group A and 109 patients (100 %) in group B, while rectal prolapse was reduced in 93 patients (85.3 %) in group A and 99 patients (90.8 %) in group B. Eleven patients in group A and 12 in group B experienced anal pain after treatment, and eight patients in group A and six in group B had mild bleeding. The patients' subjective satisfaction rates were 90.8 % in group A and 93.6 % in group B. The 1-year recurrence rates were 3.9 % in group A and 2.3 % in group B. CONCLUSIONS: Both EHL devices can effectively treat symptomatic internal hemorrhoids. A device with a smaller diameter requires more band ligations, but appears equivalent with regard to treatment outcome and complications.

Are modified procedures significantly better than conventional procedures in percutaneous transhepatic treatment for complicated right hepatolithiasis with intrahepatic biliary strictures?

BACKGROUND: Conventional percutaneous procedures for treating patients with recurrent hepatolithiasis associated with complicated intrahepatic biliary strictures require multiple dilation sessions before stone extraction. We modified the approach, reducing the number of dilation sessions required and using newer lithotripsy and irrigation methods. We suggest that the modified procedures are superior to conventional management and demonstrate their utility in clearing hepatolithiasis. METHODS: Percutaneous transhepatic stricture dilation and cholangioscopic lithotripsy were performed to treat patients with right recurrent hepatolithiasis with complicated intrahepatic biliary strictures. Conventional methods were used in 40 patients (Group A). Modified methods, including simplification of tract establishment and stricture dilation and electrohydraulic lithotripsy (EHL) were used in 60 patients (Group B). RESULTS: Group B patients had fewer complications (massive hemobilia: 0% versus 15%, P = 0.0032, cholangitis: 0% versus 17.5%, P=0.0012), tolerated the procedures better (intolerable pain: 0% versus 12.5%, P=0.0087), had a higher rate of success (residual stones: 3.3% versus 20%, P=0.0132; remaining asymptomatic and stone-free: 81% versus 50%, P = 0.0021), a shorter hospital stay (17.8 +/- 4.4 days versus 36.2 +/- 5.5 days, P < 0.001) and lower overall expense (USD 2689 versus USD 3848) than Group A patients. CONCLUSION: We believe that the modified methods are superior to conventional treatment in that they effectively decrease procedural complications and cost, and significantly improve treatment results.

Genome-wide hypomethylation in hepatocellular carcinogenesis.

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?

HYPOTHESIS: Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection. DESIGN: A case-controlled study. SETTING: A referral center. PATIENTS: Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study. INTERVENTION: Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value. MAIN OUTCOME MEASURE: The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity. RESULTS: From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively). CONCLUSIONS: Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.

Percutaneous transhepatic cholangioscopy in the treatment of complicated intrahepatic biliary strictures and hepatolithiasis with internal metallic stent.

For recurrent hepatolithiasis coexisting with a complicated long-segment intrahepatic biliary stricture, repeated surgeries, balloon dilation of the stricture, and external-internal stenting may still fail to solve the problem. We tried using a Gianturco-Rosch metallic Z internal stent (Wilson-Cook Medical, Inc., Bloomington, IN, USA) with the aid of percutaneous transhepatic cholangioscopy (PTCS) to treat such patients. Eight patients had a Z stent placed through a percutaneous transhepatic biliary drainage tract. Immediately after stent placement, PTCS was inserted via the percutaneous transhepatic biliary drainage route and a part of the wire skirt not firmly anchored in one of the eight patients was detected. It was successfully repositioned using PTCS. Recurrent cholangitis developed in three patients 6, 7, and 30 months, respectively, after stent placement. PTCS was undertaken again through a reestablished percutaneous transhepatic biliary drainage route and revealed sludge in their stent lumens. We cleared it by PTCS. No further cases of cholangitis occurred in later follow-up. PTCS is useful in ensuring adequate stent position, diagnosing and treating the causes of recurrent cholangitis, and prolonging the function of stents.

Olone modulates the therapeutic effect of interferon to eliminate preferentially the hepatitis B virus precore stop mutant.

BACKGROUND/AIMS: The aim of this study was to understand the changes in the proportion of hepatitis B virus precore stop mutant during the course of prednisolone primed interferon (IFN) therapy. METHODS: Three groups of patients were included: patients receiving prednisolone-primed IFN treatment (Group I, n=31), IFN treatment only (Group II, n=29), and placebo (Group III, n=25). The proportion of precore stop mutant was measured by a quantitative amplification-created restriction site method. RESULTS: Distinct patterns of the progression of the proportion of mutant were found among these three groups. A steady increase in the proportion of mutant was observed only in Group III patients. In Group II patients, the presence of a higher percentage of mutant (> 25%) immediately before IFN treatment was predictive for the subsequent clearance of hepatitis B e antigen (HBeAg) (p<0.01), but not for complete anti-viral response (p>0.05). Prednisolone pretreatment resulted in an increase in the proportion of mutant in patients with initially low percentages (< or = 25%) of mutant. During the period of IFN treatment, both the relative and absolute amount of the precore stop mutant decreased significantly in Group I patients who cleared HBeAg. The presence of such a decrease in this group of patients was predictive for both HBeAg clearance and complete anti-viral response. CONCLUSIONS: Our data suggest that prednisolone serves as a modulator to enhance elimination of precore stop mutant by IFN, which advocates the benefit of corticosteroid pretreatment in an area where the precore mutants are prevalent.

Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis.

The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.

Percutaneous transhepatic placement of metallic stents in the treatment of complicated intrahepatic biliary stricture with hepatolithiasis: a preliminary report.

OBJECTIVE: We aimed to study the effect of the metallic modified Gianturco-Rosch Z-stent in the management of refractory intrahepatic long-segment biliary strictures with hepatolithiasis. METHODS: Six symptomatic patients with hepatolithiasis and coexisting intrahepatic long-segment biliary strictures, who failed to respond to the silastic external-internal biliary stenting, were selected. The metallic modified Gianturco-Rosch Z-stent was placed via percutaneous transhepatic cholangiography at the strictured site. Patients were followed regularly to evaluate for recurrence of cholangitis, stones, or strictures. RESULTS: No complications were observed during the procedures. No recurrent strictures or formed calculi were found in these six patients during follow-up periods of 29 to 64 months. However, cholangitis and intrahepatic biliary muddy sludge occurred at 7 and 30 months in two patients after the placement of the metallic Z-stent. Percutaneous transhepatic cholangioscopy was used to clear sludge completely. CONCLUSIONS: Our experience suggests that the metallic stent is a well-tolerated and promising alternative in the management of refractory intrahepatic long-segment biliary strictures with hepatolithiasis. Though biliary sludge may develop, it can be detected and cleared early. Repeated surgery can thus be avoided.

Primary hepatic epithelioid hemangioendothelioma: case report.

Hepatic epithelioid hemangioendothelioma (HEH) is a very rare vascular tumor of the liver. It usually affects adult women and presents as multiple hepatic nodules with mainly peripheral distribution. It poses special difficulties for clinicians in its diagnosis and treatment because of its non-specific clinical manifestations and findings on imaging, and it is easy to be misdiagnosed pathologically. Its clinical course and prognosis are variable but supposed to be intermediate between hemangioma and angiosarcoma. The primary treatments of choice are radical resection or liver transplantation. We report a 62-year-old man with right upper quadrant abdominal pain of several days' duration, who was initially misdiagnosed as having a liver abscess. Finally, HEH was diagnosed on the basis of positive immunohistochemical staining for factor VIII-related antigen in tumor cells. This case could serve to highlight the pitfalls in diagnosing this rare tumor. Increasing the index of suspicion and familiarity with the radiological and histological characteristics of this tumor would facilitate the accurate diagnosis and thus avoid unnecessary interventions.

Are expandable metallic stents better than conventional methods for treating difficult intrahepatic biliary strictures with recurrent hepatolithiasis?

BACKGROUND: Conventional methods for treating patients with recurrent hepatolithiasis associated with complicated intrahepatic biliary strictures include balloon dilatation of the intrahepatic biliary strictures, lithotripsy, and the clearance of difficult stones as completely as possible, with the placement of an external-internal stent for at least 6 months. After these modalities are used, symptomatic refractory strictures remain. Recently we used internal Gianturco-Rosch metallic Z stents to treat patients who had refractory strictures. OBJECTIVE: To compare therapeutic results and complications of an internal expandable metallic Z stent with those of repeated external-internal stent placement. STUDY DESIGN: Case-control study. SETTING: A referral center. PATIENTS: From January 1992 to December 1996, 18 patients with recurrent hepatolithiasis and complicated intrahepatic biliary strictures underwent percutaneous dilatation of stricture and transhepatic percutaneous cholangioscopic lithotomy for recurrent stones. After their stones were completely cleared, their biliary strictures failed to dilate satisfactorily. The patients were randomly enrolled into 2 groups: group A (7 patients), who received an expandable metallic Z stent, and group B (11 patients), who had repeated placement of external-internal stents. INTERVENTIONS: Percutaneous stricture dilatation, electrohydraulic lithotripsy, balloon dilatation, percutaneous transhepatic cholangioscopic lithotomy, and biliary stenting by a Silastic external-internal catheter or a modified Gianturco-Rosch expandable metallic Z stent (for an internal stent). MAIN OUTCOME MEASURES: The number of procedures, days in hospital, procedure-related complications, incidents of stone recurrence and recurrence of cholangitis, readmissions to the hospital, treatment sessions required, and mortality rate. Patients' limitations in ordinary activities were also compared. RESULTS: The follow-up period ranged from 28 to 60 (40.7+/-12.7 [mean +/- SD]) months in group A and from 28 to 49 (36.0+/-7.2) months in group B. Fewer group A patients (3 [43%]) than group B patients (8 [73%]) tended to have recurrent cholangitis and to require readmission to the hospital, but this was not statistically significant (P = .33). When their cumulative probability of a first episode of cholangitis during follow-up was compared, however, it was significantly lower in patients treated with a metallic stent (P = .04). Compared with group B patients, group A patients had less frequent recurrence of stones (0% vs 64%; P = .01), fewer procedures for the clearance of biliary stones or sludge (1.7+/-2.2 vs 6.4+/-4.3; P = .03), and shorter hospital stays (8.0+/-11.5 days vs 17.0+/-12.0 days; P = .07). No patients in group A experienced limitation in ordinary activities, whereas 7 patients in group B did (P<.02). CONCLUSIONS: Compared with the repeated placement of external-internal stents, the use of a metallic internal stent effectively decreases stone recurrence, simplifies further procedures, and is more convenient. Its use is suggested as an alternative choice in the treatment of recurrent hepatolithiasis with refractory intrahepatic biliary strictures.

Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.

To examine the long-term effect of interferon (IFN) therapy in patients with chronic hepatitis B virus (HBV) infection, particularly on survival and hepatocellular carcinoma (HCC) prevention, 101 male patients with chronic hepatitis B in a randomized controlled trial were followed up for 1.1 to 11.5 years after the end of therapy. Of the 101 patients, 34 patients received a placebo (control), and 67 patients were treated with IFN (31 patients were treated with IFN alone and 36 patients were treated with IFN after prednisolone priming). Follow-up studies included clinical, biochemical, and virological aspects and HCC screening every 3 to 6 months. Twenty-eight (42%) of the 67 IFN-treated patients and 8 (24%) of the 34 untreated patients seroconverted by the end of the trial. During follow-up, 22 (56%) of the 39 patients who did not seroconvert in the treated group and 5 (19%) of the 26 patients who did not seroconvert in the control group showed a delayed sustained response (P <.005). The cumulative incidence of sustained response was highest in the steroid priming group (P =.049 vs. the IFN-alone group; P =.028 vs. the control group). HCC was detected in 1 (1.5%) of the 67 treated patients and 4 (12%) of the 34 untreated patients (P =.043). The interval between entry and HCC detection was 3.5 to 8.2 years. The cumulative incidence of HCC development was significantly higher in the control group than in the treated group (P =.013). In contrast, the cumulative survival rate was higher in the treated group than the control group (P =. 018). Multivariate analysis showed that IFN therapy, preexisting cirrhosis, and the patient's age at entry are significant independent factors for both survival and HCC development. The results suggest that IFN has long-term beneficial effects in terms of HBV clearance, reduction of HCC, and prolonging survival.

Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers.

OBJECTIVE: Hepatitis B, C, and delta virus (HBV, HCV, HDV) share similar transmission routes; thus, dual or triple infections may occur and even persist in the same patient. However, little is known about the presentations and course of chronic HBV infection with HCV and HDV markers, which this study examined. METHODS: Antibodies against HCV (anti-HCV) and HDV (anti-HDV) were assayed as appropriate in patients with HBV infection. The clinical, pathological, and virological presentations as well as the course of the disease in patients with HBV/HDV/HCV triple infection markers were then reviewed. RESULTS: A total of 60 patients, 51 men and nine women, age 19-67 yr (mean 45.9+/-1.6 yr) were identified. Of these 60 patients, five (8.3%) were HBeAg positive and 10 (16.7%) cirrhotic at entry, 30 (50%) presented with acute superinfection (HCV or HDV, or both) and the remaining 30 presented with chronic liver disease. On presentation, 16 (53.3%) of the 30 patients with acute superinfection showed hepatic decompensation and eight (26.7%) died. In contrast, only one of the patients with "chronic liver disease" presented with hepatic decompensation. Of the 42 patients followed up for 1-15 (mean, 4.7+/-0.6) yr, 45.2% showed remission and 19% showed HBsAg seroclearance, whereas 12.5% of the 32 noncirrhotics developed cirrhosis and three of the nine cirrhotics became decompensated. At the end of follow-up, 29 patients (69.9%) were still seropositive for HCV-RNA but only nine (22.5%) were seropositive for HDV-RNA and five (12.5%) were seropositive for HBV-DNA. CONCLUSIONS: These results suggest that infection with HBV, HCV, and HDV triple markers is a severe disease in acute superinfection stage but that the course is relatively benign, slowly progressive, and usually dominated by HCV.