Transjugular intrahepatic portosystemic shunt after adult liver transplantation: experience in eight patients.

BACKGROUND: Transjugular intrahepatic portosystemic shunting (TIPS) has become an effective treatment for the complications of portal hypertension. We assessed the feasibility and outcome of TIPS in liver transplant recipients. METHODS: During the period from December 1992 to January 1998, eight adults presenting recurrent hepatitis C virus (five patients) and hepatitis B virus (one patient) infection, veno-occlusive disease (one patient), and secondary biliary cirrhosis (one patient) had TIPS because of refractory ascites (five patients), bleeding esophageal varices (one patient), refractory hepatic hydrothorax (one patient), retransplantation (two patients), and redo-biliary surgery (one patient). RESULTS: In two patients, the procedure was difficult due to cavo-caval implantation. Ascites, hydrothorax, and variceal bleeding were controlled in all patients. Moderate to severe encephalopathy developed in four patients; two patients had worsening of their existing encephalopathy. Three of five patients treated with cyclosporine needed a drastic dose reduction due to the development of severe side effects. No long-term survivor developed shunt stenosis or occlusion. Two patients did moderately well at 6 and 14 months, respectively; the former died due to chronic rejection while waiting for a retransplantation. Three did well at 14, 36, and 28 months, respectively; the latter patient died of liver failure 32 months after TIPS. One jaundiced patient died after 1.5 months due to necrotic pancreatitis. Two patients died after 4 and 8.5 months, respectively, due to liver failure; the latter was doing well until 7 months after TIPS. CONCLUSIONS: TIPS is feasible in transplant recipients in cases of decompensated allograft cirrhosis, of allograft veno-occlusive disease or when retransplantation or redo-biliary surgery are scheduled in the presence of portal hypertension. At transplantation, the surgeon should keep in mind the eventuality of a later TIPS procedure. Close immunosuppression monitoring is warranted because modified metabolization of cyclosporine (and probably tacrolimus) may cause serious side effects.

Short report: interferon-alpha decreases 14C-aminopyrine breath test values in patients with chronic hepatitis C.

OBJECTIVE: To investigate the effect of interferon-alpha on cytochrome P-450 dependent microsomal function. METHODS: The 14C-aminopyrine breath test was performed before, during and after a standard dose of interferon-alpha (3,000,000 units three times per week) was administered for at least six months (nine patients with chronic hepatitis C). RESULTS: Mean aminopyrine breath test values obtained during therapy were significantly lower than either pre- or post-treatment, the degree of reduction varying widely between individuals. Pre- and post-treatment aminopyrine breath test values did not differ significantly. CONCLUSION: Interferon therapy is associated with a significant and transient inhibition of cytochrome P-450 activity, which should be taken into account when prescribing concurrent therapy with drugs metabolized by this pathway.

[Primary biliary cirrhosis: current modes of presentation. Clinical, biochemical, immunologic and histologic study of 206 patients seen from 1978 to 1988]. / La cirrhose biliaire primitive: modes actuels de présentation. Etude clinique, biochimique, immunologique et histologique de 206 malades observés de 1978 à 1988.

The aim of this study, based on a series of 206 patients (186 women and 20 men) with primary biliary cirrhosis seen from 1978 to 1988, was to assess the current modes of presentation of the disease. In approximately 30 percent of patients, primary biliary cirrhosis was recognized at an asymptomatic stage. Two thirds of these patients remained asymptomatic: they were older (mean age 57 years) and had less severe histological lesions than the patients who became symptomatic (mean age 45 years). The modes of presentation were not markedly different in the male and female patients of our series. The prevalence of cholelithiasis seemed to be particularly high (more than 20 percent in our patients). Complications of portal hypertension (bleeding esophageal varices or ascites) were the initial manifestations of primary biliary cirrhosis in 8 percent of our symptomatic patients. Alkaline phosphatase level was normal or only slightly increased in 15 percent of our patients: a normal level or a slight increase in alkaline phosphatases is not an argument against the diagnosis of primary biliary cirrhosis. Antinuclear antibodies with perinuclear fluorescence were demonstrated in 26 percent of our patients; in most of these patients, an antibody to a 200 kD protein of the nuclear envelope was present; in patients with this antibody, asthenia, arthralgias and associated extrahepatic diseases were less common and the titers of antibodies to mitochondria were lower than in the patients without this antibody.

[Fulminant or sub-fulminant hepatocellular failure caused by metastatic invasiveness of the liver: an other cause of hypoxic hepatitis?]. / Insuffisance hépatocellulaire fulminante ou subfulminante secondaire à une infiltration métastatique du foie: une autre cause d'hépatite hypoxique?

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

Fatal hypoxic hepatitis in a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease).

Hypoxic (ischemic) hepatitis generally requires the concurrence of an underlying condition which chronically exposes the liver to some degree of hypoxia (for example, congestive heart failure) combined with a triggering event (for example, arrhythmia) which further decreases the oxygen supply. We report a case of hypoxic hepatitis in which hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease) constituted this underlying condition and gastrointestinal hemorrhage was the triggering event. To our knowledge, this is the first reported case of hypoxic hepatitis in hereditary hemorrhagic telangiectasia with the exception of therapeutic ligation or embolization of the hepatic artery so as to decrease shunting of liver blood. Hemodynamic mechanisms are proposed to explain this particular outcome.

A randomized, open-label, multicenter study evaluating the efficacy of peginterferon alfa-2a versus interferon alfa-2a, in combination with ribavirin, in naïve and relapsed chronic hepatitis C patients.

BACKGROUND/AIMS: A large multicenter trial to compare the efficacy of peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in chronic hepatitis C patients. Efficacy data for prior relapsers are reported because treatment recommendations for this patient population are not well defined. PATIENTS AND METHODS: This study was a multicenter, prospective, randomized clinical trial. The primary efficacy endpoint was sustained virologic response in naive patients (n = 348) and relapsers (n = 95). RESULTS: Sustained virologic response rates were similar in naïve patients and relapsers, both for non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%). Pegylated interferon given for 48 weeks did not improved the relapse rate: 15.9 and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naïve vs relapsers respectively. Stepwise logistic regression analysis revealed a significant association between slow response (detectable HCV RNA at week 12 and undetectable at week 24) and relapse in patients with an end-of-treatment response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). CONCLUSIONS: This trial confirms the value of using peginterferon alfa-2a in both naïve and relapsed patients and provides support for a more tailored approach to treatment for relapsers and particulary for patients with a slow viral response.

Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients.

BACKGROUND: The combination therapy of pegylated-interferon-alpha2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40-50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. AIM: To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. METHODS: In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-alpha2a (180 microg once weekly) plus ribavirin (1000-1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. RESULTS: There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. CONCLUSIONS: This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients.

Portal vein thrombosis as the first sign of a primary myeloproliferative disorder: diagnostic interest of the V617F JAK-2 mutation. A report of 2 cases.

Portal vein thrombosis is, in some cases, related to a myeloproliferative disorder but the diagnosis of the latent forms may be difficult in case of normal blood counts. We report two cases of patient with portal vein thrombosis of unknown origin in whom the presence of the V617F mutation of the Janus Kinase 2 gene lead to the diagnosis of primary myeloproliferative disorder, confirmed on bone marrow examination. The search of the V617F mutation of the Janus Kinase 2 gene has to be performed in all cases of portal vein thrombosis of unknown origin.

Weekly pegylated interferon alpha-2b vs daily interferon a-2b versus standard regimen of interferon a-2b in the treatment of patients with chronic hepatitis C virus infection.

BACKGROUND AND STUDY AIMS: The combination of Pegylated (PEG)interferon alpha-2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A : daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B : PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin; Group C: interferon alfa-2b at a dose of 3 MIU TIW + ribavirin PATIENTS AND METHODS: Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A: daily interferon alpha-2b (4 MIU s.c. for patients > 65 kg or 0.06 MIU/kg < 65 kg) and ribavirin, group B: PEG-interferon alpha-2b (100 microg s.c. weekly for patients > 65 kg or 1.5 microg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm) : interferon alpha-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis; 78 never started treatment (35 in group A, 28 in group B and 15 in group C): 101 in group A, 98 in group B and 59 in group C. RESULTS: Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38% of drop-outs were due to adverse events compared to 37% in group B and 58% in group C. No statistical differences were observed regarding safety. CONCLUSION: Daily weight based interferon alpha-2b dosing and PEG interferon alpha-2b weighed based dosing once weekly both in combination with Ribavirin offer the same efficacy and safety rates.

Feasibility, safety and cost-effectiveness of transjugular liver biopsy following major surgery in patients with haemophilia.

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of patients with haemophilia became infected with the hepatitis C virus. Although transjugular liver biopsy can be safely performed in these patients, the procedure is associated with a significant financial burden mainly related to replacement therapy with clotting factor. The purpose of this study was to evaluate the feasibility and safety of transjugular liver biopsy in patients with haemophilia substituted with clotting factor concentrates for major surgical procedures. Over the last 5 years, transjugular liver biopsy was performed in nine patients with haemophilia within 1-10 days after orthopaedic (7), thoracic (1) or abdominal surgery (1). All patients had abnormal liver function tests and persistent hepatitis C viraemia. At the time of the biopsy, patients received recombinant factor VIII delivered by dose-adjusted continuous infusion through a central catheter inserted preoperatively in the left internal jugular (n = 8) or in an ante-cubital vein (n = 1). Before the biopsy, basal FVIII levels were raised to 80-100% by a bolus infusion and maintained above 80% for 24 h. The biopsy was informative in all cases. Only one patient developed an episode of supraventricular dysrhythmia. No bleeding or infectious complications were observed. When compared with elective liver biopsy performed outside the postsurgical period, the cost-savings per biopsy were 19 875 +/- 2660 euro. This study shows that intensive replacement therapy required by surgical procedures provides a safe and cost-effective opportunity for transjugular liver biopsy in patients with haemophilia and active hepatitis C.

Black pigments in the liver related to gold and titanium deposits. A report of four cases.

Black pigments are rarely described in the liver. We report four patients with chronic cholestasis and black pigments described on liver histological examination. Energy-dispersive X-ray analysis identified these black pigments as gold particles in the first three patients and titanium particles in the fourth. The origin of the gold deposits was unknown in this first patient and related to gold salts therapy in the two others. Titanium deposits was associated with hepatic granulomas and related to total knee replacement.

The HepCar registry: report on a one-year registration program of hepatocellular carcinoma (HCC) in Belgium. What is daily practice in HCC?

INTRODUCTION: Due to a rise in HCV induced liver cirrhosis, hepatocellular carcinoma becomes more prevalent in Western European countries. The HepCar registry is an initiative in which patients with hepatocellular carcinoma, their treatment and follow up are registered. MATERIALS AND METHODS: Belgian physicians were asked to report all new cases of hepatocellular carcinoma which were seen between January 2003 and December 2003. Reporting was done on a voluntary basis. Data reported were: demographic figures, the nature of the underlying liver disease, presentation characteristics of the tumour, laboratory findings and choice of therapy. Every six months, a reminder was sent to determine survival. RESULTS: 131 patients (94 male/37 female) were reported. Mean age was 63 years +/- 13. Underlying liver disease was HCV (n = 54, 41%), HBV (n = 22, 17%), alcoholic liver disease (n = 39, 30%) and miscellaneous (n =16, 12%). Diagnosis of hepatocellular carcinoma was made by surveillance in 47 (36%) patients. After logistic regression, survival was 5 times better for patients inside the Milan criteria (one lesion less than 5 cm in diameter or less than 3 nodules each less than 3 cm in the absence of vascular invasion and metastasis). DISCUSSION: Tumours inside the Milan criteria have a better survival. The majority of the patients have an underlying cirrhosis as background for the development of a HCC.

The management of patients with mild hepatitis C.

Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver disease. However, the identification of these patients with mild hepatitis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are persistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probability of response and the motivation of the patient.

[Current contribution of molecular biology in the diagnosis of hepatitis B]. / Apports récents de la biologie moléculaire dans le diagnostic des hépatites dues au virus B.

Recent advances in molecular biology had led to a better understanding of the pathology of hepatitis B virus. The polymerase chain reaction technique has shown that the genome of hepatitis B virus is highly variable. Mutations in the pre-core region are associated with HBe Ag negative chronic hepatitis and fulminant hepatitis B; moreover, rare cases of hepatitis due to HBV with mutations within the S gene have been reported in HBV-vaccinated patients. The aim of this paper is to assess the clinical, serological and therapeutic features of hepatitis B variants.

Practical management of patients treated with alpha interferon.

Interferon alpha is currently used in chronic hepatitis and side effects are well known. They always must be kept in mind to start and to follow a patient under this therapy. A large number of autoantibodies may appear during interferon therapy, usually without clinical manifestations. The detection of dysthyroidism, requires measurement of antithyroid antibodies and TSH before and during interferon therapy. Exacerbation of chronic liver disease under IFN may be found in case of seroconversion in a patient with hepatitis B cirrhosis or in patient with a misdiagnosis of autoimmune hepatitis. Neurolopsychological disturbances are frequently reported; most of them spontaneously disappear. However, depression must be detected because of the risk of attempted or successful suicide. Worsening or sudden onset of psoriasis or lichen planus have been reported in patients treated with interferon. Appearance or aggravation of some clinical symptoms and biochemical tests may threaten life's patient under IFN therapy. The decision to maintain or to interrupt therapy should take into account the response to interferon and the severity of side effect.

[Chronic viral hepatitis and interferons: preliminary results in 60 patients with chronic hepatitis C and cellular mechanism of action]. / Hépatites chroniques virales et interférons: résultats préliminaires chez 60 patients porteurs d'une hépatite chronique C et mécanismes d'action cellulaire.

Interferons exhibit antiviral and immunomodulatory properties. Antiviral effects appear mainly mediated via 2'5' oligoadenylate synthetase and protein kinase proteins which inhibit viral components synthesis. Interferons also influence the immune system through various mechanism among whom an increased expression of HLA class I antigens on hepatocyte plasma membrane and the promotion of natural killer cell activity leading to the clearance of infected hepatocytes. We report the results of various alpha interferon therapeutic regimens in 60 patients with chronic hepatitis C. In our series, 20 patients (33%) achieved a complete response but 78% of them relapsed after therapy withdrawal. Predictors of good response include young age, low serum ALT levels and mild liver injury. On the contrary, cirrhosis is associated with a poorer response.

Treatment of hepatitis C: impact on the virus, quality of life and the natural history.

Results of treatment for chronic hepatitis C have improved substantially during the last decade. Combination treatment with interferon alpha 3 MU tiw and ribavirin 1000-1200 mg daily during 24 to 48 weeks leads to sustained virologic response (SVR) in approximately 40% of patients, two to three times more than interferon alpha monotherapy. It was considered standard therapy at the EASL Consensus Conference of February 1999. Recently, results have been published on treatment with pegylated interferons alone and in combination with ribavirin. Pegylated interferon treatment leads to almost doubling of SVR rate as compared with standard interferon monotherapy. Combination of pegylated interferon alpha with ribavirin is most promising, leading to a SVR rate of 54 to 56%. It is to be expected that this treatment will become the new standard. Selected patients with geno-type 2 or 3 have now a SVR rate of almost 80%. Response to treatment also leads to significant improvement of quality of life and survival, probably by reducing the risk of developing hepatocellular carcinoma. Recent data suggest that early interferon alpha treatment of patients with acute hepatitis C largely prevents the development of chronicity.

Symptomatic ileocolic fistula as a complication of endoscopic laser therapy. A case report.

Since 1973, laser photo therapy is used in the treatment of gastrointestinal neoplasms as well as in various forms of intestinal hemorrhage. Complications including hemorrhage, stenosis and perforation are well documented but ileocolic fistulas after laser therapy for a villous adenoma have been rarely reported. We report the case of a patient with diarrhea related to an ileocecal fistula. This fistula appeared 1 year after laser therapy for a villous tumor of the cecum.

Spontaneous exoneration of a colonic lipoma.

Colonic lipoma is a rare tumor. This tumor is usually asymptomatic. We report the case of a patient who complained of abdominal pain. Symptoms disappeared after spontaneous exoneration of a colonic lipoma.