Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0-->> 4.2, p=0.000) ; lactulose group (11.3-->> 5.0, p=0.000) ). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Efficacy and Safety of Large Volume Paracentesis in Cirrhotic Patients with Spontaneous Bacterial Peritonitis: A Randomized Prospective Study / 대한간학회지

BACKGROUND/AIMS: Large volume paracentesis (LVP) associated with plasma volume expansion is known to be an effective and safe therapy for tense or refractory ascites in cirrhosis. Spontaneous bacterial peritonitis (SBP) is one of the frequent infections in patients with cirrhosis. We conducted a study to assess the efficacy and safety of large volume paracentesis in cirrhotic patients with SBP. METHODS: We randomly assigned 40 patients with cirrhosis and SBP to either treatment with LVP (21 patients) or general management (19 patients). LVP was defined as drainage of ascitic fluid of more than 4 liters in a single tap or loss of shifting dullness after paracentesis. LVP was performed within 48 hours after the diagnosis of SBP in the LVP group. Cefotaxime was given daily in doses that varied according to the serum creatinine level in both groups. Albumin was given at a dose of 6-8 g per 1 liter of removed ascites in the LVP group. RESULTS: After seven days of treatments, the blood chemistry test, and WBC (PMN) counts and protein concentration in the ascitic fluid were not different between the two groups. Among them, the WBC (PMN) counts were decreased significantly in both groups and protein concentrations tended to increase. Durations of abdominal tenderness and pain were shorter in the LVP group but the differences were statistically not significant. Admission periods, resolution rates of SBP after seven days of treatment, complication rates and in-hospital mortality rates were not different between the two groups. CONCLUSIONS:: The two treatment methods demonstrated almost the same effectiveness and safety. The symptoms were improved slightly faster in the LVP group. We concluded that large volume paracentesis is not an absolute contraindication and can be a tolerable and safe therapy in some selected cirrhotic patients with tense ascites and SBP.

A Case of Spontaneous Necrosis of Hepatocellular Carcinoma after Development of Pneumonia / 대한간학회지

Spontaneous regression of hepatocellular carcinoma is an extraordinarily rare phenomenon. Fewer than 20 occasions have been reported in the English medical literature. There have only been 5 case reports in Korea. Understanding of the mechanism of spontaneous regression of hepatocellular carcinoma will help us to establish new treatments for the disease. In this case report, we present a 53 year-old Asian male who showed spontaneous necrosis of hepatocellular carcinoma confirmed with pathology. He developed a febrile condition secondary to pneumonia for 2 weeks. After that hepatocellular carcinoma was observed to have been necrosed on an MRI scan and hepatic angiography. A right lobectomy of the liver was done because the possibility of residual microscopic cancer cells could not be ruled out. The pathologic finding confirmed the spontaneous near-total necrosis of hepatocellular carcinoma. The patient has recovered uneventfully and has been followed up for 7 months.

Efficacy and Safety of Short-term Administration of Rifaximin in the Treatment of Hepatic Encephalopathy / 대한간학회지

BACKGROUND/AIMS: A prospective, randomized study was performed to evaluate the efficacy and safety of the short-term administration of rifaximin in the treatment of hepatic encephalopathy. METHODS: Of the 64 patients diagnosed as having decompensated liver cirrhosis with hepatic encephalopathy, 39 patients were randomized to receive rifaximin and 25 patients to receive lactulose for seven days. Before and after the treatment we assessed changes in the level of serum ammonia, flapping tremor, patient's mental status, number connection test (NCT), and hepatic encephalopathy indices. RESULTS: In rifaximin-treated group, the mean grade of serum ammonia (1.8->0.9), mental status (1.3->0.3), NCT (3.0->2.0), and flapping tremor (1.7->0.4) were improved after treatment. In the lactulose-treated group, the mean grade of serum ammonia (1.9->1.0), mental status (1.5->0.5), NCT (3.3->2.1), and flapping tremor (1.4->0.3) were improved after treatment. Side effects of abdominal pain (rifaximin group) and excessive diarrhea (lactulose group) were noted in 2 cases. The efficacy of treatment was not significantly different between rifaximin and lactulose-treated groups (84.3% vs. 95.3%). CONCLUSION: Rifaximin was as efficient and safe in the treatment of hepatic encephalopathy as lactulose in terms of efficacy. Rifaximin may be useful drug for the short-term treatment of hepatic encephalopathy.

Histopathologic Correlation between Chronic Hepatitis B and Nephropathy / 대한간학회지

BACKGROUNDS/AIMS: The relationship between HBV infection and nephropathy has been reported with some differences according to the investigators and regions studied. Liver biopsies were not performed in most of the reports. In this study both liver and kidney biopsies were performed. The histologic correlation was analyzed between chronic B viral hepatitis and nephropathy. METHODS: From January 1985 to June 2000, both liver and kidney biopsies were performed on 26 patients who had chronic hepatitis B, proteinuria, and hematuria. Also, a new histopathologic classification of chronic hepatitis was applied in the assessment of liver disease. RESULT: Light microscopy of kidneys showed IgA nephropathy in 7 cases (27%); minimal change nephrotic syndrome (MCNS) in 1 case (3.8%); and membranous glomerulonephritis (MGN) in 9 cases (34.6%), membranoproliferative glomerulonephritis (MPGN) in 9 cases (34.6%). Among the cases with a higher hepatitis activity index and fibrosis score, the frequency of MGN and MPGN was higher. The hepatitis activity index of cases with MGN was significantly higher than IgA nephropathy and MPGN (p=0.011, p=0.039). The fibrosis score of cases with MGN and MPGN was significantly higher than IgA nephropathy (p=0.011, p=0.003). The positivity of HBeAg was highest in cases with MGN. Serum C3 level was low in all cases but the serum C4 level was within normal range. Immunofluorescence studies showed granular deposition of IgG and C3 in the capillary loops in MGN. CONCLUSION: The frequency of MGN and MPGN was higher when the liver disease was more severe. It was suggested that HBeAg, IgG and C3 might contribute to the pathogenesis of MGN in HBsAg positve patients.

Prospective Study on Efficacy of Oral Supplement of Branched-Chain Amino Acid Granules on the Nutritional Status of the Cirrhotics / 대한간학회지

BACKGROUND/AIMS: A prospective comparative study was conducted to investigate the efficacy of orally administered branched-chain amino acids (BCAA) in cirrhotic patients. METHODS: Forty-seven patients with liver cirrhosis of viral etiologies, whose hypoalbuminemia could not be corrected with adequate protein intake, were randomly assigned to either the BCAA group (n=31) or the control group (n=16). The selection criteria were ages between 16 and 70 years, patients whose Child-Pugh scores were less than 13 points and who were willing to participate in the study. Most patients (87.1%) belonged to Child-Pugh class B. Patients in the BCAA group received oral supplementation with branched-chain amino acid granules (12 g/day, each packet containing total 4 g of BCAA, i.e. leucine, 1904 mg; valine, 1144 mg; isoleucine, 952 mg) for 12 weeks. Patients had complete blood counts and chemistry at entry and once every month. Serum ferritin and amino acid concentrations in plasma were determined. Anthropometric parameters including body weight, body fat contents and body mass index were assessed at the beginning and at the end of the 3-month period. RESULTS: In the BCAA group, there was a significant increment in plasma levels of isoleucine, valine (p < 0.001) whereas levels of aromatic amino acids did not show substantial change. Total BCAA concentration and BCAA/AAA (aromatic amino acid) molar ratio (Fischer's ratio) also increased significantly after the administration of oral BCAA (p < 0.001). In contrast, patients in the control group showed no significant change in assessed parameters. CONCLUSION: Oral supplementation of BCAA to cirrhotic patients improved several parameters reflecting nutritional status without causing encephalopathy or other serious adverse effects.

Clinical Implication of Automatically Analysed AFP-L3 and PIVKA-II in the Diagnosis of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Prothrombin induced by Vitamin K Antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) subtype reacting with Lens Culinaris Agglutinin (AFP-L3) are known as specific tumor markers for HCC. Recently a more sensitive EIA method for PIVKA-II and an automatic analyzer with Liquid Phase Binding Assay method (LBA method) for AFP-L3 have been developed. The aim of this study was to evaluate the feasibility of PIVKA-II and AFP-L3 measured by newly developed methods as complementary tumor markers to AFP in the diagnosis of HCC. METHODS: The serum concentration of AFP, PIVKA-II, and a fraction of AFP-L3 were determined from 188 patients with HCC and 118 patients with various liver diseases including 46 with liver cirrhosis, 10 with chronic hepatitis, 50 with metastatic liver cancers, and 12 with benign tumors of the liver. AFP was measured by EIA, PIVKA-II by sensitive EIA, and AFP-L3 by the LBA method with LiBASys Auto-analyzer. The cutoff values for AFP, PIVKA-II, and AFP-L3 were 400 ng/mL, 40 mAU/mL, and 15%, respectively. RESULTS: The sensitivity and specificity of serum PIVKA-II were 69.2% and 76.5%, respectively. Sixty-two (51.2%) of 121 patients with HCC, in which AFP was less than 400 ng/mL were PIVKA-II positive. The sensitivity and specificity of serum AFP-L3 were 48.8% and 90.8%, respectively. When AFP-L3 was used in combination with PIVKA-II, 31 (46.3%) of the 67 patients with small less than 3 cm HCC were positive for at least one of these markers. CONCLUSION: PIVKA-II measured by sensitive EIA may be useful for the diagnosis of HCC with low AFP level. AFP-L3 and PIVKA-II may improve the detection rate of small HCCs less than 3 cm.

Treatment Outcome and Prognostic Factors in Patients with Advanced Hepatocellular Carcinoma (TNM Stage IVa) according to Anticancer drugs of Transhepatic Arterial Chemoinfusion / 대한간학회지

BACKGROUND/AIMS: The study proposed to evaluate the efficacy of anticancer drugs of intraarterial chemoinfusion and investigate prognostic factors influencing survival. METHODS: A total of 127 patients diagnosed as having advanced hepatocellular carcinoma(HCC) of same stage (TNM stage IVa) from 1996 to 1998 were examined. Two intraarterial infusion chemotherapeutic regimens were employed: Adriamycin(Group I) and Cisplatin(Group II). RESULTS: Overall survival was significantly diffrent(10.0 vs 5.7months) and favored Group I. By the univariate analysis, significant prognostic factors included: age, portal vein thrombosis(PVT), size(>5cm) and type of tumor, response rate (size & -fetoprotein) at 3 months after therapy, level of albumin, alkaline phosphatase, and total bilirubin. After repeated therapy, Group I showed better survival (14.0 vs 7.9 months), but there was no statistical difference in survival rate between two groups in the case of large size, PVT, and diffuse type. CONCLUSION: Group I showed better survival than Group II in advanced HCC of TNM stage IVa. But, considering prognostic factors, there was no significant difference in survival rate between two groups except small size or nodular type of HCC. TNM classification of stage IVa should be reconsidered to include prognostic factors influencing survival rate such as PVT, size and type of HCC.

Endoscopic Transpapillary Biopsy for the Diagnosis of Patients with Pancreaticobiliary Ductal Strictures / 대한소화기내시경학회지

BACKGROUND AND AIMS: Many diseases and conditions are responsible for pancreaticobiliary ductal strictures. In such patients, histologic diagnosis is crucial to determine therapeutic modalities and to predict their outcomes, as well as to avoid unnecessary operations for tissue diagnosis. To evaluate the diagnostic role of endoscopic transpapillary biopsys (ETPB), this technique was performed in patients with pancreaticobiliary ductal strictures suggestive of malignancy. METHODS: After visualization of the pancreaticobiliary tree and the lesion by endoscopic retrograde cholangiopancreatography (ERCP), an ETPB of the lesion was conducted with or without an endoscopic sphincterotomy (EST) in sixty-four patients with pancreaticobiliary ductal strictures. The biopsy results were analysed according to the morphology of the lesion, site of the stricture, number of biopsys and whether or not an EST was done. RESULTS: The final diagnoses of the sixty-four patients included forty bile duct cancers (62.5%), nine pancreatic cancers (14.1%), four metastatic cancers (6.3%), and eleven benign ductal strictures (17.2%) such as biliary stones, cholangitis, etc. The sites of the strictures were located in the upper bile duct in thirty-two patients (50.0%), the middle bile duct in twenty-two (34.4%), the lower bile duct in three (4.7%), the pancreatic head in four (6.3%), and the pancreatic body in three (4.7%). Adequate tissue specimens for pathologic examination were obtained in fifty-four cases (84.4%). An ETPB was possible without an EST in nineteen cases (29.7%). The ETPB results revealed sensitivity of 60.4% (32/53), specificity of 100% (6/6), positive predictive value of 100% (32/32), and negative predictive value of 34.4% (11/32). The sensitivity of the ETPB was higher in the EST group than in group without an EST. There was no statistical significance however, according to tumor morphology, site, or number of biopsys. CONCLUSIONS: It is recommended that an ETPB, being a safe and effective method, should be performed as a diagnostic procedure during an ERCP for patients with pancreaticobiliary ductal strictures of unknown causes.

A Case of Wegener's granulomatosis with obstruction of both anterior tibial and peroneal arteries / 결핵

Wegener's granulomatosis is characterized by necrotizing granulomatous vasculitis affecting upper and lower respiratory tracts and kidneys. Vascular lesions commonly involve capillaries and small vessels but, less commonly larger vessels. We report a 46-year-old male patient of Wegener's granulomatosis associated with paranasal sinusitis, pulmonary consolidations, glomerulonephritis, skin lesions with obstruction of both anterior tibial and peroneal arteries. Several necrotic lesions of the toes had progressed to gangrene and both transmetatarsal amputations were done. The patient continued to receive cyclophosphamide and prednisolone.

A Case of Wegener's granulomatosis with obstruction of both anterior tibial and peroneal arteries / 결핵

Wegener's granulomatosis is characterized by necrotizing granulomatous vasculitis affecting upper and lower respiratory tracts and kidneys. Vascular lesions commonly involve capillaries and small vessels but, less commonly larger vessels. We report a 46-year-old male patient of Wegener's granulomatosis associated with paranasal sinusitis, pulmonary consolidations, glomerulonephritis, skin lesions with obstruction of both anterior tibial and peroneal arteries. Several necrotic lesions of the toes had progressed to gangrene and both transmetatarsal amputations were done. The patient continued to receive cyclophosphamide and prednisolone.

Clinical Usefulness of ERCP in Acute Pancreatitis / 대한소화기내시경학회지

The safety of endoscopic retrograde cholangiopancreatography(ERCP) in patients with acute pancreatitis(AP) was confirmed in the past decade. Especially in ease of acute gallstone panereatitis, early ERCP/EST(endoscopic sphincterotomy) may reduce the incidence of complications by removing gallstone which causes acute attack of pancreatitis. To assess clinical usefulness of ERCP/EST in the setting of AP, we reviewed clinical records of 58 patients with AP who had undergone ERCP /EST during the same period of admission.(continue...)

Duodenal Varices Causing Massive Upper Gastrointestinal Hemorrhage / 대한소화기내시경학회지

The bleeding duodenal varices are a rare complication in patients with portal hypertension, but present a difficult diagnostic problem. If there is no bleeding esophageal, gastric fundal varices or ulcer in a patient with upper gastrointestinal bleeding and portal hypertension, the possibility of bleeding duodenal varices should be kept in mind. Thorough endoscopic examination of the entire duodenal mucosa is essential to document bleeding from duodenal varices. As an initial treatment, endoscopic sclerotherapy has had limited success in controlling active duodenal variceal bleeding. However, rebleeding rate is high, surgical treatment including shunt operation may be required for permanent control of bleeding and portal decompression. We report three cases of duodenal varices causing massive hemorrhage. All the patients had portal hypertension caused by liver cirrhosis of various etiologies and had varices in their esophagus. The second portion of the duodenum was the site of duodenal varices in all cases. The management was tailored to the condition of each patient, but only one patient among three survived.

Treatment outcome of the patients with small hepatoma (5 cm in diameter) in relation to treatment modalities and underlying liver function / 대한간학회지

BACKGROUND/AIMS: To compare treatment outcome of hepatocellular carcinoma(HCC) under the size of 5 cm in relation to underlying liver function and treatment modalities, analysis of data from 145 patients was performed. METHODS: In this study, the records of 145 patients with small HCC (40 ng/mL) serum alpha-fetoprotein(AFP) level. Liver cirrhosis was associated in 109(75.2%) patients. Sixty five(44.8%) patients underwent surge, 63(43.5%) underwent transarterial therapy(TAT), 8(5.5%) underwent other modalities of therapy and the remaining 9(6.2% ) patients did not receive any specific treatment for HCC. In relation to the underlying liver function, 119(82.1% ) patients belonged to the non-cirrhotic or Child-Pugh class A, 20(13.8%) to class B and 6(4.1%) to class C. The median follow-up duration was 21 months. When analyzed with respect to treatment modalities alone, median survival was 43 months for all patients, 60 months for surgery, 29 months for TAT, 20 months for other treatment and 18 months for patients who received no specific treatment. Without considering liver function, cumulative 3 year survival rate was 68.6% for surgery, 43.9% for TAT, 29.2% for other treatment and 0% for no treatment. The survival rate for the patients who underwent surgery was significantly higher than for any other treatment modalities without considering the underlying liver function or in the non-cirrhotic/Child-Pugh class A(p0.05). But in patients classified as the non-cirrhotic/Child-Pugh class A, better survival was observed in the surgep group than the TAT group(p<0.05). The only factor influencing survival was the pre-treatment serum AFP level(p<0.05). The overall recurrence rate was 30.3%. For the entire patients, the factor significantly influencing the recurrence rate was the presence of underlying cirrhosis. When considering only the patients in the surgery group, the different types of surgical procedures significantly influenced the recurrence rate. CONCLUSION: Surgery is the treatment of choice for patients with HCC equal to or smaller than 5 cm. But for those patients whose tumor size is less than 3 cm, TAT may be a reasonable alternative to surgep when the liver function is not adequate for hepatic resection. Because overall recurrence rate exceeded 30% and median time of recurrence was only 9.5 months after definitive treatment, careful follow-up is required for all patients who undergo treatment for small HCC.

A Case of Lymphangioma of the Large Intestine Removed by Colonoscopic Polypectomy / 대한소화기내시경학회지

Lymphangioma occuring in the gastrointestinal tract is a rare benign tumor, which is composed of lymphatic vessels of various size. A sharply demarcated smooth, soft, cystic submucosal tumor which is easily compressible and covered with normal mucosa is a characteristic eadoscapic feature. Recently, we experienced a case of lymphangioma in ascendmg colon and removed it successfully by colonoscopic snare polypectomy.