Alessandro Pezzoli

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis

BACKGROUND/AIMS The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication. METHODS The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A). RESULTS Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders. CONCLUSIONS These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.

Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial

OBJECTIVES:The aims of this long-term, prospective randomized study were to evaluate the clinical usefulness of α-interferon in treating chronic HBV infection and to establish whether clearance of viral replication markers and normalization of liver function tests induced by α-interferon were sustained.METHODS:Sixty-four patients with chronic wild type (HBeAg-positive) hepatitis B, enrolled between 1983 and 1987, were randomized into two groups. Thirty-three patients received α-interferon (5 MU/m2 three times weekly for 6 months; treated group), and 31 were not treated (controls). Treated and control patients were prospectively followed for a mean of 86.4 ± 6.96 and 79.7 ± 6.8 (p= NS) months, respectively.RESULTS:Clearance of the following viral markers was found in treated and control patients as follows: HBV-DNA, 26 (78.9%) and 18 (58.1%) (p= 0.106); HBeAg, 30 (90.9%) and 19 (61.2%) (p < 0.007); and HBsAg, 12 (36.4%) and three (9.8%) (p < 0.017). Persistent abnormal ALT levels were found in 11 (33.3%) treated and in 22 (70.9%) control patients (p < 0.025). Four control and three treated patients developed portal hypertension whereas two control and one treated patient developed hepatocellular carcinoma. Seven patients (five treated and two controls) were retrospectively found to have hepatitis C virus (HCV) coinfection before enrollment. To date, all coinfected patients remain positive for HCV-RNA. Also, all HCV coinfected patients, except one in the treated group, had persistent increased serum ALT levels. One of the coinfected patients developed portal hypertension.CONCLUSIONS:Chronic HBV hepatitis patients responding to interferon treatment had a faster, more complete, and sustained clearance of viral markers than controls; HCV coinfection does not seem to negatively affect the clearance of HBV replicative markers. However when coinfection occurs, hepatic disease persists despite HBV marker clearance.

Interobserver agreement in describing video capsule endoscopy findings: a multicentre prospective study.

BACKGROUND AND AIM Few studies have specifically addressed interobserver agreement in describing lesions identified during capsule endoscopy. The aim of our study is to evaluate interobserver agreement in the description of capsule endoscopy findings. MATERIALS AND METHODS Consecutive short segments of capsule endoscopy were prospectively observed by 8 investigators. Seventy-five videos were prepared by an external investigator (gold standard). The description of the findings was reported by the investigators using the same validated and standardized capsule endoscopy structured terminology. The agreement was assessed using Cohens kappa statistic. RESULTS As concerns the ability to detect a lesion, the agreement with the gold standard was moderate (kappa 0.48), as well as the agreement relating to the final diagnosis (κ 0.45). The best agreement was observed in identifying the presence of active bleeding (κ 0.72), whereas the poorest agreement concerned the lesion size (κ 0.32). The agreement with the GS was significantly better in endoscopists with higher case/volume of capsule endoscopy per year. Diagnostic concordance was better in the presence of angiectasia than in the presence of polyps or ulcers/erosions. CONCLUSIONS Correct lesion identification and diagnosis seem more likely to occur in presence of angiectasia, and for readers with more experience in capsule endoscopy reading.

Efficacy of ursodeoxycholic acid in association with α-interferon for chronic hepatitis C in α-interferon non-responder patients

BACKGROUND The aim of the present study was to evaluate the effect of combined treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to alpha-IFN alone. METHOD One hundred and three patients (60 men, 43 women, mean age 49 +/- 1.3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha-IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal yGT, genotype distribution and liver histology, while mean age was lower in controls (53 +/- 1.8 vs 46 +/- 1.8 years; P< 0.01). RESULTS Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P< 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P= NS) and HCV-RNA was still undetectable in four of them. Portal and periportal inflammation showed a statistically significant improvement (Fishers exact test P< 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. CONCLUSIONS These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance.

Asymptomatic bronchial aspiration and prolonged retention of a capsule endoscope: a case report

IntroductionCapsule endoscopy has, over the last few years, become a first-line test to visualize the mucosa of the small intestine. This technique is generally considered safe and does not cause discomfort for patients. However, although patients may have difficulty in swallowing the capsule, bronchial aspiration of a capsule endoscope is a very rare complication. We report the case of an 82-year-old man who experienced prolonged bronchial aspiration of a capsule endoscope without relevant symptoms, followed by a spontaneous return of the capsule to the gastrointestinal tract.Case presentationAn 82-year-old Caucasian man was referred to our unit from another local hospital to undergo capsule endoscopy. He swallowed the capsule without any apparent difficulties and did not show any overt symptoms. The following day, when we reviewed the capsule endoscopy images, we realized that the capsule was in the bronchial system and remained there for the duration of the study. An urgent X-ray of the chest confirmed the presence of the capsule in the left side of the bronchopulmonary tree. Two days later a repeat chest X-ray showed the capsule in the right bronchus. After two days the capsule was retrieved in the feces. Our patient remained asymptomatic during the entire admission period.ConclusionsAspiration of a capsule endoscope is a rare complication; to the best of our knowledge this is the first reported case in which a capsule endoscope remained for six days in the bronchial system of a patient without causing airway compromise or pneumonitis and spontaneously returned to the gastrointestinal tract.

Methylprednisolone Administration in Primary Biliary Cirrhosis Increases Cholic Acid Turnover, Synthesis, and Deoxycholate Concentration in Bile

As immunosuppressive agents, corticosteroids maybe considered an appropriate treatment for primarybiliary cirrhosis, even if bone loss and other sideeffects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologicallyproven primary biliary cirrhosis (stage I-IV). Weadministered methylprednisolone (24 mg daily) for 30days to ascertain its effects on biliary lipidmetabolism, which are largely still unknown. All patientsunderwent a 30-day drug-washout period before enteringthe trial. The following parameters were studied beforeand after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kineticsand synthesis; biliary lipid secretion; biliary bileacid pattern; biliary lipid molar percentage; andcholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon ranktest) increase in cholic acid turnover (from 0.26± 0.04 to 0.50 ± 0.05 K/day, P = 0.005)and synthesis (from 0.42 ± 0.12 to 0.78 ±0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molarpercentage (from 19.4 ± 2.7 to 30.6 ± 4.4%molar, P = 0.01). On the other hand, a significantdecrease in biliary cholesterol molar percentage (from7.9 ± 0.7 to 6.4 ± 0.5 % molar, P =0.005), cholesterol saturation index (from 1.11 ±0.11 to 0.95 ± 0.07, P = 0.05), and biliarycholesterol secretion (from 64.7 ± 5.4 to 53.0± 4.5 μmol/hr, P = 0.005) was observed. These findings show thatshort-term administration of methylprednisolone inpatients with primary biliary cirrhosis does not induceexpansion of the cholic acid pool but increases cholicacid synthesis and turnover, as well as intestinalproduction of deoxycholic acid. If long-term treatmentis considered, the beneficial immunosuppressive effectsof corticosteroids have to be weighed against the hepatotoxic properties of deoxycholicacid.

Portal hypertensive enteropathy diagnosed by capsule endoscopy and demonstration of the ileal changes after transjugular intrahepatic portosystemic shunt placement: a case report

IntroductionRecent data suggest that mucosal abnormalities can occur even in the duodenum, jejunum, and distal ileum of cirrhosis patients. We present a case of portal hypertensive enteropathy in a cirrhosis patient shown by capsule endoscopy and the effect of transjugular intrahepatic portosystemic shunt on the ileal pictures.Case presentationAn 83-year-old Caucasian woman was admitted to our hospital for anemia and a positive fecal occult blood test. An upper gastrointestinal endoscopy revealed small varices without bleeding signs and hypertensive gastropathy. Colonoscopy was negative. To rule out any other cause of bleeding, capsule endoscopy was performed; capsule endoscopy revealed severe hyperemia of the jejunum-ileal mucosa with active bleeding. Because of the persistence of anemia and the frequent blood transfusions, not responding to β-blocker drugs or octreotide infusion, a transjugular intrahepatic portosystemic shunt was performed. Anemia improved quickly after the transjugular intrahepatic portosystemic shunt, and no further blood transfusion was necessary in the follow-up. The patient developed portal encephalopathy two months later and was readmitted to our department. We repeated the capsule endoscopy that showed a significant improvement of the gastric and ileal mucosa without any signs of bleeding.ConclusionHypertensive enteropathy is a rare condition, but it seems more common with the introduction of capsule endoscopy in clinical practice. This case shows that the jejunum can be a source of bleeding in cirrhosis patients, and this is the first demonstration of its resolution after transjugular intrahepatic portosystemic shunt placement.

Unexpected finding after gastroduodenal artery embolization

An 87-year-old woman with melena and anemia was admitted to the hospital and underwent urgent GI endoscopy. During the procedure, a large clot adhering to the posterior wall of the duodenal bulb was identified. Its removal with a retrieval net revealed an underlying visible vessel with active oozing (A). After an ineffective attempt to obtain endoscopic hemostasis with epinephrine injection, argon plasma coagulation, and clips, interventional radiology was performed. Selective arteriography of the celiac trunk revealed no extravasation, so blind embolization of the gastroduodenal arterywith 3 platinumcoils (SPIRALES.01800, coilB 3 mm, coil length 5 cm; Balt Extrusion, Montmorency, France) was carried out (B, continous arrow: coil; dashed arrow: clip). Hemostasis was achieved, and the patient’s subsequent clinical course was uneventful. Three months later, the patient returned to the hospital with epigastric pain and vomiting. Upper GI endoscopy revealed a foreign body (a metallic coil) protruding from the posterior wall of the duodenal bulb. The adjacent mucosa

Pharmacological Treatment of Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is a rare hepatic disorder, but its incidence is increasing. It is chronic and progressive, eventually leading to the development of cirrhosis. During the course of the disease, symptoms such as pruritus and asthenia may appear. At present, the only successful treatment for PBC is liver transplantation. While no pharmaceutical treatment is truly effective, some newer drugs, or new combinations of these drugs, have given some promising results. In this chapter, the efficacy of the more important pharmacological agents in use, as well as some currently under study, are examined in terms of laboratory parameters, symptoms, end points, histological presentation and natural history of the disease.