Evidence Of Varices Research Articles

Real-world multicentre analysis of patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (A+B): Efficacy, esophagogastroduodenoscopy (EGD) uptake and bleeding complications.

4105 Background: The IMbrave150 trial established A+B as a standard of care for HCC and an EGD within 6 months (mos) of starting treatment to detect esophagogastric varices and prevent bleeding complications was advised. However, the value of performing EGD in all patients (pts) is unknown. Methods: We conducted a retrospective analysis of all HCC pts treated with A+B between July 2020 to August 2022 at 5 cancer centres from the Canadian provinces of Ontario, Alberta and Manitoba (members of the HCC-CHORD Consortium). Pts characteristics and treatment history including efficacy, EGD details and bleeding events were collected. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated. A comparative analysis was conducted to compare the correlation between the EGD uptake and bleeding events. Results: A total of 112 pts were identified (median age 66 years, 87% male, 24% East Asian, 67% liver cirrhosis, 33% HCV, 25% HBV, 15% NASH, 23% BCLC B, 71% BCLC C, 91% Child-Pugh A, 29% main portal vein invasion, 45% ALBI grade 1 and 54% ALBI grade 2). Prior to systemic, 61% had locoregional therapies. 90% received A+B as first-line therapy, while 9% received it as second-line and 1% as third-line. Outcomes of pts treated with A+B are shown. Before starting A+B, 78 pts (70%) had completed an EGD within 6 mos. Of these, 32 pts (41%) had evidence of varices on EGD, and 15 (20%) required treatment with either banding or beta-blockers. All bleeding events in this population was 15% (n=17). Bleeding rates in the EGD and non-EGD groups were 18% (n=14) and 9% (n=3), respectively. Bleeding adverse events were 5%(n=6) gastrointestinal vs 10%(n=11) non-gastrointestinal (6 epistaxis, 1 ecchymosis, 1 periodontal and 3 unspecified). The GI bleeding rates in the EGD and non-EGD groups were 6% (n=5) and 3% (n=1). Conclusions: Outcomes of HCC pts treated with A+B in Canada are comparable to those observed in the IMbrave150 trial. Our study detected and treated varices at twice the rate of the IMbrave150 trial among the EGD group, reflecting real-world treatment of a high-risk population. Yet, pts who had no EGD before starting A+B, presumably due to a low risk of portal hypertension based on physicians’ judgement, did not experience more bleeding/GI bleeding than those who had an EGD. This supports the approach of selective EGD prior to A+B, and more guidelines are needed in this area. Outcomes and response rate of patients(pts) treated with Atezolizumab with Bevacizumab in this study. [Table: see text]

S3649 Choroidal Melanoma: A Rare Cause of Gastric/Duodenal Pigmented Macules

Introduction: Choroidal melanoma is the most common primary intraocular malignancy. Two to four percent of newly diagnosed patients have evidence of metastatic disease. Up to half of patients will develop metastatic disease. The liver is the primary site of metastasis as the tumor spreads hematogenously. Metastasis to the gastrointestinal tract is rare in ocular melanoma in contrast to cutaneous melanoma. We present a case of ocular melanoma with metastasis to the gastrointestinal (GI) tract. Case Description/Methods: An 81-year-old female with a history of choroidal melanoma of the left eye diagnosed in 2015 treated with radiotherapy presented to the hospital with fatigue and weight loss of 30 pounds over the last few months. On admission she was normotensive and afebrile. On physical exam her abdomen was distended and nontender. Labs were notable for Cr 2.3 mg/dL, AST 698 IU/L, ALT 286 IU/L, ALP 488 IU/L, Albumin 2.3 g/dL, Total bilirubin 4.9 mg/dL, WBC 13.3 K/uL, Hgb 11.7 g/dL, platelets 206 K/uL and INR 1.6. Computed tomography without contrast of the abdomen/pelvis showed lobular contour of the liver with multiple hyperdense foci scattered throughout concerning for metastases. Ultrasound with dopplers revealed portal vein thrombosis. Patient underwent endoscopy for variceal screening with no evidence of varices. However, scattered throughout the stomach were hyperpigmented macules of variable size (a, b). In her duodenum, there were additional lesions (c) and two non-bleeding ulcers with pigmented lesions. Biopsies were consistent with metastatic melanoma. Ultimately, hospice was pursued. Discussion: Choroidal melanoma metastases in the GI tract are rare. When patients with a history of melanoma, regardless of its origin, present with nonspecific symptoms, physicians should have a high suspicion for metastatic disease. Metastases are endoscopically diagnosed as pigmented or amelanotic nodules, ulcerations, macules or mass. Patients are typically treated with palliative surgery or immunotherapy. Prognosis is typically poor with a median survival rate of 4 to 6 months.Figure 1.: Endoscopic images of hyperpigmented lesions in the stomach (a, b) and duodenum (c).

S2866 Rectal Variceal Hemorrhage Requiring Treatment With Endoscopic Band Ligation

Introduction: Acute variceal hemorrhage is a gastrointestinal emergency and a major cause of death in cirrhotics. We present a rare case of rectal variceal hemorrhage causing clinically significant bleeding. Case Description/Methods: A 38 year old with alcohol use disorder presented with jaundice and confusion. He was ill-appearing, unable to follow commands, with scleral icterus, abdominal distention with positive fluid wave and anasarca. He had a hemoglobin of 3.7 g/dL, platelet count of 100 K/mcL, creatinine of 1.9 mg/dL, total bilirubin of 36.3 mg/dL, lactate of 9.9 mmol/L, ammonia of 82 mcmol/L and INR of 4.3. Computed tomography of the abdomen and pelvis with contrast showed a cirrhotic appearing liver, portal venous hypertension, moderate ascites and mesenteric varices. He was transfused 2 units of packed red blood cells (pRBC) with improvement in hemoglobin to 7 and initiated on treatment for decompensated cirrhosis. Gastroenterology was consulted with esophagogastroduodenoscopy (EGD) finding grade D esophagitis without evidence of varices or ulcerations. Despite lactulose and rifaximin, his encephalopathy worsened and he was intubated for airway protection. His stool became increasingly saturated with blood and his hemoglobin continued to downtrend, requiring a total of 9 units of pRBCs over the course of 4 days. A repeat EGD found no varices. Colonoscopy was performed which revealed 5 tortuous bleeding rectal varices that were band ligated. Transfusion requirements dramatically decreased post-procedure. (Figure) Discussion: Due to rarity, there are no established guidelines for treatment of rectal varices as opposed to esophageal varices. Unlike bleeding gastroesophageal varices, no randomized control trials have shown proven benefit for use of vasoactive drugs such as octreotide in bleeding rectal varices. Management of rectal varices can include methods involving endoscopy, interventional radiology or surgery. One retrospective study showed that endoscopic injection sclerotherapy has greater efficacy compared to endoscopic band ligation with less rebleeding rate. However, another study showed endoscopic band ligation to be superior. Additional procedures such as transjugular intrahepatic portosystemic shunt with or without embolization and balloon-occluded retrograde transvenous obliteration have also demonstrated resolution of acute bleeding. Failure of these methods leads to surgical treatment such as suture ligation and porto-caval shunt. We achieved hemostasis with endoscopic variceal ligation.Figure 1.: Colonoscopy images showing bleeding rectal varices.

The Predictors Of Re-Bleeding In Chronic Liver Disease Patients After Endoscopic Variceal Band Ligation.

Variceal bleeding is a key and most fatal complication observed in chronic liver disease patients with portal hypertension and is a major contributor to the high morbidity and mortality seen in these patients. Exploring the predictors of rebleeding in chronic liver disease patients is of paramount importance to alter disease course and impact on morbidity and mortality. About 50 patients with chronic liver disease who previously had evidence of varices on upper GI endoscopy and had at least one episode of rebleeding after EVBL were included in this study. Patients were assessed for the possible contributors to rebleeding through complete history, clinical examination, coagulation profile and platelet count, ultrasound features (splenic size and portal pressure), and upper GI endoscopic findings (site and grade of varices, red sign). Sample selection was done using non-probability purposive sampling technique and sample size calculated using the standard WHO formula. Data was entered and analyzed using SPSS version 20. In this study, mean age of the patients was 51.34±6.34 years with male predominance (64%). Rebleeding was significantly associated with grade of varices, presence of red sign on upper GI endoscopy, site of varices, splenic size and coagulopathy. Rebleeding in chronic liver disease patients following EVBL is predicted by grade, extent and site of varices, red sign on upper GI endoscopy, splenic size and coagulation disturbances.

Outcomes of Patients with Budd-Chiari Syndrome and Factors Predicting the Need for TIPS & Liver Transplantation - a Single-Center Long-Term Experience

Background: Budd-Chiari Syndrome (BCS) is a complex thrombotic disorder caused due to obstruction of hepatic venous outflow involving anywhere from small hepatic venules to the entrance of inferior vena cava into the right atrium. This leads to venous stasis and ischemic injury of hepatic parenchyma and sinusoids, with the risk of liver failure. The prognosis of patients with BCS had improved significantly with long-term anticoagulation and measures like Trans-Jugular-Intrahepatic-Porto-Systemic shunt (TIPS) and liver transplantation. We report the outcomes of patients who follow in our hematology practice and describe the factors predicting the need for TIPS/Liver Transplant.Methods: After appropriate Investigational Review Board permission, we identified patients with a history of BCS following in our thrombosis clinical practice from the year 2010 onwards. We evaluated their laboratory, demographic, anticoagulation data, Model of End-stage Liver Disease (MELD) score, Child-Pugh (CP) score at diagnosis or when earliest available, and other relevant clinical information as outlined. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported. Further, we compared the two categories of patients who needed TIPS/Liver transplants versus those who did not. SAS version 9.4 was used for analysis. For continuous variables, a univariate nonparametric Mann-Whitney test was used. The Fisher's Exact Test was used to associate each variable with the need for TIPS/Liver Transplant.Results: Our study included 23 patients with baseline characteristics, including median age of 36 years (11-59 years), 91% whites, 61% females, 44% smokers, 61% obese(median BMI 29.9 kg/m 2), 6 of 14 women on oral contraceptive pills, 22% with thrombosis history, 17% with stroke history, median hemoglobin 13.4 gm/dL(8.9-20 gm/dL), white blood cell count 9,400/L (3,050-31,500/L), platelet count 294,000/L(14,000-767,000/L), serum creatinine 0.87 mg/L (0.55-2.52 mg/dL), total protein 6.3 gm/dL (5.2-8.8 gm/dL), Bilirubin 2.1 mg/dL(0.1-20.2 mg/dL), Aspartate Aminotransferase (AST) 61 U/L(16-1037 U/L), Alanine Aminotransferase (ALT) 43U/L(18-1694 U/L), MELD score 15 (range 7-38), CP score 9 (5-14), 74% with cirrhosis, 82% with ascites at one point, 57% with myeloproliferative neoplasm (MPN), 4.3% with Paroxysmal Nocturnal Hemoglobinuria (PNH), 17% with Antiphospholipid antibodies positive (APS), 13% had positive antinuclear antibodies, 35% needed TIPS and 44% required liver transplantation. 57% with Janus Kinase (JAK2) V617F mutation (1 patient with a low variant allele frequency of 1%), 1 patient (4.3%) had Calreticulin (CALR) mutation positive MPN, 91% remained on long-term anticoagulation with 40% using warfarin, 35% apixaban, 9% Enoxaparin or Rivaroxaban for long-term anticoagulation, 13% developed heparin-induced thrombocytopenia (HIT). 8.7% had developed BCS after Ad26.COV2.S vaccine to prevent SARS-CoV-2 infection. Excluding the patients with missing variables, 5 of 12 had Protein C deficiency, 3 or 10 had Protein S deficiency, 8 of 20 with Antithrombin (AT) deficiency, 4 of 14 with heterozygous factor V Leiden mutation, 0 of 10 with prothrombin gene mutation, 1 of 13 with hyper-homocysteinemia. 35% had gastrointestinal bleeding though 65% of patients had evidence of varices by endoscopy. When the group needing TIPS/Liver transplant/died is compared to those who did not, they had higher bilirubin, MELD, PC score, AT deficiency, cirrhosis, ascites, and JAK2 mutation (p-value significant: Table 1). With a median follow-up of 90 months, overall survival was not statistically significant between the two groups (Figure 1). Two patients (8.7%) died out of a total of 23.Conclusions: Our data indicate that in patients with BCS, neoplasms (61%), particularly MPN (57%), are very commonly diagnosed. Compared to the historical data in patients with BCS with dismal prognosis (60-80% six-month mortality rate), the overall survival had significantly improved, likely due to supportive measures like TIPS/Liver transplant and long-term anticoagulation. Outside the established variables like CP and MELD, lower antithrombin activity and positive JAK2 mutation status also predicted a higher TIPS/Liver transplant need. [Display omitted] DisclosuresBhatt: Partnership for health analytic research, LLC: Consultancy; Abbvie: Consultancy, Research Funding; Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Gundabolu: BioMarin Pharmaceuticals: Consultancy; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Company: Consultancy; Pfizer: Research Funding; Samus Therapeutics: Research Funding.

PWE-046 Comparison of Transient Elastography, Thrombocytopenia and Splenomegaly in Risk Assessment for The Presence of Oesophageal Varices: Abstract PWE-046 Table 1

Introduction The usage of transient elastography (TE) as a predictor of oesophageal varices has been widely studied. The formation of varices is the sequelae of portal hypertension (PH) which also manifest as splenomegaly leading to thrombocytopenia. We aim to establish the utility of TE in conjunction with PH in predicting varices. Methods Patients who underwent TE with the FibroScan® between June 2010 and January 2016 in our trust were identified. Only patients with a liver stiffness measurement (LSM) of >11.5 kPa which is indicative of cirrhosis and had undergone an endoscopy were included. Thrombocytopenia was defined as a platelet count of 25 kPa has been regarded as the optimum cut-off value for predicting varices and is used in this study. Results 2,643 patients underwent TE during the time period. 372 patients had a LSM of >11.5 kPa and of these patients, 157 patients underwent a gastroscopy. 41 patients (26.1%) had evidence of varices on gastroscopy. The sensitivity and specificity of TE in various combinations of PH in predicting varices are outlined in the table below. In total 46 out of our 157 patients with cirrhosis had TE Conclusion In our cohort of patients, a cut-off value of >25 kPa on TE is a better predictor of varices (sensitivity 83%) than thrombocytopenia or splenomegaly. Assessment of LSM using TE in conjunction with thrombocytopenia and splenomegaly improves sensitivity further to 97%. Limiting screening endoscopy in patients with liver cirrhosis to those with any of those 3 criteria: TE > 25 kPA, thrombocytopenia or splenomegaly, may reduce demand for endoscopy in that group of patients by 30%. Disclosure of Interest None Declared

Study of the Relationship between Blood Ammonia Level and Esophageal Varices in Patients with Liver Cirrhosis

Background and study aim : Portal hypertension leads to formation of portosystemic collateral veins as oesophageal varices in patients with liver cirrhosis. Several studies have shown that blood ammonia is a vauable non invasive marker of oesophageal varices. This study is designed to evaluate the possible relation between blood ammonia level and oesophageal varices in patients with liver cirrhosis. . Patients and Methods: This study was conducted on three groups of patients and control subjects. Group I included 20 cirrhotic patients without evidence of oesophageal varices. Group II included 40 cirrhotic patients with evidence of varices. Group III included 20 healthy control subjects. Serum level of ammonia were done for all patients and control subjects. Results: There was a highly significant increase in the mean values of blood ammonia in cirrhotic patients with varices in comparison to other patients without varices, with highly significant positive correlation between serum ammonia and size of varices. There was a significant increase in the mean values of blood ammonia in cirrhotic patients with grade III and IV varices [large varices) in comparison to cirrhotic patients with grade I and II varices. Conclusion:Blood ammonia level is a valuable, simple non invasive marker for prediction of oesophageal varices.

Evaluation of Venous Ammonia Level, Splenic Longitudinal Diameter, Portal Vein and Splenic Vein Diameters as Non-Invasive Indicators for the Presence of Portosystemic Collaterals in Egyptian Cirrhotic Patients

Introduction and Aim of the Work: The identification of cirrhotic patients with esophageal varices or other portosystemic collateral by non-invasive means is appealing in that it could decrease the necessity of endoscopic screening. This study was to evaluate the diagnostic utility of venous ammonia level with other ultrasonographic parameters as non-invasive markers for the presence of portosystemic shunts. Patients and methods: The study included 3 groups of Child Pugh class A and early B patients. Group (A): 25 patients with evidence of both esophageal varices and portosystemic collaterals; group (B) 25 patients with neither evidence of varices nor portosystemic collaterals and group (C): 25 patients with evidence of varices but no collaterals. Measurement of venous ammonia level was done for all patients. Results: serum ammonia level was significantly higher in group A (222.8 ± 54 μg/dL) than that in group B (85 ± 21.1 μg/dL) and group C (148.2 ± 19.6 μg/dL). The cut-off value of serum ammonia level 113 μg/dL was a good predictor for the presence of esophageal varices, while the cut-off value of serum ammonia level at 133 μg/dL was a good predictor for the presence of both esophageal varices and abdominal collaterals. Combination of portal vein diameter > 13mm + splenic vein diameter > 8.9mm + ammonia level > 133 μg/dL gives 100% of sensitivity and 96% of specificity for the prediction of the presence of portosystemic shunts. Conclusion: Determination of serum ammonia level, splenic, portal vein and splenic vein diameters are considered as good predictors for the presence of portosystemic shunts in patients with liver cirrhosis.

Natural history of small duct primary sclerosing cholangitis: a case series with review of the literature

Information about the natural history of small duct primary sclerosing cholangitis (SDPSC) remains scant despite literature suggesting that it constitutes 6-16% of all cases of primary sclerosing cholangitis (PSC). We combined clinical data on SDPSC cases from two tertiary care institutions with liver transplantation programs with the aim of studying the natural history of SDPSC. Medical records of 25 individuals with SDPSC were reviewed. Diagnosis of SDPSC was based on liver biopsy findings consistent with PSC, a normal cholangiogram, and elimination of known causes of secondary sclerosing cholangitis. Demographic information, symptoms, past medical history, laboratory values, and histologic data were evaluated. Our primary outcome measure was liver transplantation or death. Secondary outcome measures included evidence of end-stage liver disease, development of cholangiocarcinoma, and/or the development of classic PSC on a repeat cholangiogram. Data on 25 individuals (13 males, 12 females; mean age 40±15years) diagnosed with SDPSC were analyzed. Upon presentation, 11 patients had symptoms including abdominal pain, fatigue, and pruritus. Inflammatory bowel disease was present in 14 patients (56%) at diagnosis. On initial liver biopsy, 60% had early-stage disease (I or II) and none had cirrhosis. On follow-up (1-168months, median 17months), malignancy or progression to classic large duct PSC was not noted. Two (8%) patients had evidence of varices and one of the two also developed ascites; one of these patients underwent liver transplantation and the other one died due to sepsis. SDPSC, a mild disease at presentation typically runs a benign course and likely is not an early stage of classic PSC. Further studies with a control group of classic PSC and longer follow-up are needed to study the natural history of SDPSC.

Pylephlebitis complicating silent diverticulitis

In December, 2005, a 70-year-old, previously healthy, man was admitted with a 1-week history of fever and pain in the upper abdomen without nausea or vomiting. On physical examination, he was febrile (39·5°C) and had rigors; blood pressure was 90/60 mmHg, pulse was 90 bpm, and he had epigastric and right upper quadrant tenderness. Laboratory test results showed leucocytosis of 11·2×10/L (neutrophils 89%), normochromic normocytic anaemia (Hb 112 g/L), high erythrocyte sedimentation rate (124 mm/h) and C-reactive protein (277 mg/L), and a total bilirubin of 27·7 μmol/L with a conjugated value of 15·7 μmol/L. Other laboratory tests for liver function were normal. An urgent contrastenhanced CT of the abdomen was unremarkable. We treated the patient with broad-spectrum intravenous antibiotics (imipenem and vancomycin). On the second day of admission, MRI showed thrombosis of the left branch of the portal vein (fi gure A), and several diverticulae and signs of diverticulitis in the left colon (fi gure B); no biliary dilatation was seen. On further questioning, the patient denied any symptoms of constipation, low abdominal pain, or bloody stools. Two blood cultures grew Clostridium tertium. Doppler ultrasonography confi rmed the occlusion of the left portal vein branch. No evidence of varices were found on oesophagogastroduodenoscopy. Colonoscopy confi rmed the presence of multiple diverticulae as well as mucosal oedema in the sigmoid colon. His fever and abdominal pain subsided on days 5 and 6 of admission, respectively. He was started on low molecular weight heparin and then switched to oral warfarin. Further laboratory tests for a hypercoagulable state were negative. He completed a 4-week course of intravenous antibiotics (imipenem and vancomycin) and a 3-month course of oral anticoagulation. Out-patient doppler ultrasonography 1 month after the initiation of anticoagulation therapy showed complete resolution of the clot. When seen for follow-up in June, 2006, the patient was in excellent health. Pylephlebitis, or septic thrombophlebitis, of the portal vein represents a previously under-diagnosed condition with a uniform mortality in the pre-antibiotic era. It is usually secondary to infections in the region drained by the portal system, and is most commonly associated with appendicitis and diverticulitis, but it has also been described in necrotising pancreatitis, infl ammatory bowel disease, haemorrhoidal disease, foreign body perforation, acute cholecystitis, Behcet’s disease, and amoebic colitis. The usual clinical fi ndings include fever and right upper quadrant pain without jaundice. Doppler ultrasonography, MRI, and contrast CT are all considered sensitive imaging techniques for diagnosis, although no comparative evidence exists. Multiple liver abscesses may complicate the course of the disease. An interaction between the infectious agent and the endothelium may precipitate the clotting cascade and result in portal vein thrombosis. Anaerobic infections are usually associated with thrombotic diseases because certain bacterial components may enhance fi brin clotting and heparin degradation. The role of anticoagulation is controversial, because no randomised studies addressing this issue exist. In a retrospective study of 44 cases, patients who received anticoagulation therapy had a better outcome than those who did not. However, it was reported that in patients with normal clotting function and isolated thrombosis of the portal vein, anticoagulation may be unnecessary. In the absence of consensus, anticoagulation treatment was empirically administered in our patient. A high index of suspicion for pylephlebitis is required in patients with any septic abdominal event and right upper quadrant pain without jaundice—even in the absence of clinical signs from the primary site of infection. Modern imaging techniques facilitate early diagnosis in cases that probably remained undiagnosed in the past due to poor visualisation of the portal vein. Prompt administration of antibiotics in this situation should be considered life saving.

Beta Blocker Prophylaxis for Patients With Variceal Hemorrhage

To characterize beta blocker therapy for the primary and secondary prevention of variceal hemorrhage. Variceal hemorrhage is one of the more frequent and severe complications of portal hypertension due to liver disease. Beta blocker therapy has been demonstrated to decrease risk of first bleed in patients with evidence of varices and recurrent bleeding and mortality in patients with history of prior variceal hemorrhage. A total of 106 patients with liver disease hospitalized with suspected variceal hemorrhage were retrospectively reviewed. Half of patients had known varices, 44 (41.5%) of whom had experienced prior variceal hemorrhage. Only 21 (20%) were receiving beta blocker therapy at admission and 41 (48%) at discharge. The majority were not receiving therapy for primary prophylaxis (94%). Specific characteristics associated with beta blocker use could not be identified, although more patients with history of greater than two variceal hemorrhages were receiving beta blocker at admission (73% vs. 41%, P = 0.04) This study suggests that liver disease patients with varices are often not receiving beta blocker therapy to reduce risk of first or subsequent variceal hemorrhage. Opportunity exists to optimize use of this proven prophylactic treatment and bridge an apparent gap in standard of care.

Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6‐thioguanine during maintenance therapy

6-Thioguanine (TG) was recently studied to determine whether TG in maintenance therapy achieves better event free survival than 6-mercaptopurine (MP) for standard risk acute lymphoblastic leukemia (ALL) on the clinical trial, CCG-1952 (5/1996-1/2000). Veno-occlusive disease was previously recognized as a complication of TG on CCG-1952. We report a newly recognized pediatric complication of TG: splenomegaly and portal hypertension (PH) developing during maintenance or after completion of therapy. Twelve patients (3-10 years) had been randomized to receive a targeted dose of 50 mg/m(2)/day of TG during maintenance phases. Actual TG dose ranged from 25 to 77 mg/m(2)/day (median 34 mg/m(2)/day). The initial patient, a boy who had marked thrombocytopenia and intermittent splenomegaly during maintenance therapy, was evaluated for persistent pancytopenia and progressive splenomegaly 3 months after completion of therapy. Dilated splenic vein and collaterals consistent with PH were documented by MRI/MRA. Esophagogastroduodenoscopy found esophageal varices. Liver biopsy showed periportal fibrosis and marked dilatation of veins and venules. Of the other 12 patients, 9 patients studied had abnormal MRI/MRAs with evidence of varices in 4. Eight patients had splenomegaly on physical examination. Liver biopsies in a girl after 3.3 courses of TG and a boy after 4.6 courses of TG showed periportal fibrosis and dilatation of venules and sinusoids and minimal focal fatty changes. Subsequent MRI/MRAs have been stable or improved. The evaluations of these 12 patients suggest that treatment with TG causes injury to the liver leading to PH and that thrombocytopenia and splenomegaly are clinical hallmarks of this toxicity.

Clinical, biochemical and histological features in 102 patients with chronic hepatitis C virus infection

The clinical, biochemical and histological features of 102 consecutively referred patients with chronic hepatitis C virus infection were analysed. Demographic, epidemiological, biochemical, haematological and histological details were catalogued for each patient. The mean follow-up was 49 +/- 6 months. Liver biopsies were obtained from 92 patients; a second biopsy was obtained from 35 patients. The average known duration of infection was 8.6 +/- 0.7 years. The most common risk factors that could be identified were past blood transfusion, surgery or intravenous drug abuse. Twenty-four of the 27 patients (85%) with past blood transfusion had received blood in countries outside of northern Europe. In contrast, 12 of the 16 former drug users were northern European. Patients were frequently diagnosed incidentally; one-quarter had no symptoms of liver disease and were generally asymptomatic or had presented with non-specific complaints and were found to have abnormal serum aminotransferase levels after routine screening. The mean serum aminotransferase levels were not significantly different in those presenting with fatigue compared to those diagnosed incidentally. The most common physical sign in these patients was a palpable liver, which was present in 52%. The mean serum albumin concentration in patients older than 40 years was significantly lower than that in younger patients. Splenomegaly and endoscopic evidence of varices was also more common in older patients. Cirrhosis was present in 37% of patients at presentation: 20% showed progression on rebiopsy, and 5% developed cirrhosis within 4 years of initial presentation. Of those treated, 27% showed histological improvement. Histological severity did not correlate with duration of disease, but did correlate with age.(ABSTRACT TRUNCATED AT 250 WORDS)