The Effect of Hepatitis B Virus on Graft and Overall Survival in Kidney Transplant Patients.

OBJECTIVES: We investigated the effect of hepatitis B virus in kidney transplant patients in terms of patient care and survival. MATERIALS AND METHODS: We retrospectively analyzed kidney transplant patients from 1993 to 2013. A control group with negative serology was selected. The hepatitis B virus-positive group was divided into 2 subgroups based on serologic status, treatments, and treatment responses. Group A had viral suppression, and group B had hepatitis B virus DNA persistence. Overall and allograft survival rates were compared. RESULTS: We identified 32 hepatitis B virus-positive and 74 hepatitis B virus-negative patients. Positive group was treated with lamivudine (n = 23), lamivudine plus entecavir (n = 4), lamivudine plus tenofovir (n = 4), or lamivudine plus entecavir and tenofovir (n = 1). In group A (n = 15), antiviral treatment was given based on the presence of either hepatitis B surface antigen with negative hepatitis B virus DNA (n = 11) or hepatitis B virus DNA positivity (n = 4). Group B patients (n = 17) received antiviral treatment for persistence of hepatitis B virus DNA (n = 7) or for viral reactivation (ie, recurrence of hepatitis B virus DNA) (n = 10). Groups A and B did not differ significantly in terms of graft or overall survival. Liver biopsy was performed in 17 patients; 3 patients had high-grade fibrosis or cirrhosis, and 14 patients had normal histology or mild hepatitis. Median graft survival time was longer in positive group (69.5 mo vs 54 mo; P = .007). Five- and 10-year overall survival rates were comparable (89%-84% vs 96%-96%; P = .107). CONCLUSIONS: Hepatitis B virus-positive kidney transplant patients have increased liver transaminase levels, longer graft survival times, and similar median overall survival rates compared with hepatitis B virus-negative patients.

Significance of Colonoscopic Findings in Patients After Kidney Graft.

OBJECTIVES: We aimed to investigate the colonoscopy findings in patients after kidney transplant. MATERIALS AND METHODS: We retrospectively analyzed kidney transplant patients who had colonoscopy examinations for various indications between 2011 and 2015. RESULTS: Eighty-one patients (25 women and 56 men) with a mean age of 39 years (range, 18-64 y) were identified. Mean follow-up after transplant was 9 years (range, 1-29 y). The most common indications for colonoscopy were diarrhea (41%), anemia (29%), gastrointestinal bleeding (12%), abdominal pain (12%), and unexplained weight loss (6%). Either colitis or ileitis or both were diagnosed in 20 patients (25%), whereas polyps were found in 9 patients (11%). One patient presented with hematochezia, which was diagnosed as cytomegalovirus colitis. The remaining cases of colitis or ileitis were diagnosed as nonspecific inflammation. Indications for colonoscopy were not correlated with age, duration after transplant, or use of immunosuppressive drugs. A subgroup analysis for mycophenolate-induced colitis found that 88% of patients used mycophenolate, but presence of colitis or ileitis had no statistical correlation with its use. In patients with poor gastrointestinal symptoms, the only significant predictor of presence of colitis or ileitis was a high C-reactive protein value (> 5 mg/dL; P = .02). CONCLUSIONS: Incidence of colitis and/or ileitis is a relatively common finding in patients after kidney transplant. Opportunistic infections, mycophenolate use, and mild degree of indeterminate colitis or ileitis disease may be the underlying condition. Cytomegalovirus infection should be screened in all recipients because it may cause serious complications or death in chronically immunocompromised patients.

Endoscopic Retrograde Cholangiopancreatography in Kidney Transplant Patients: Results From a Single Center.

OBJECTIVES: We report the outcomes of endoscopic retrograde cholangiopancreatography procedures performed for diagnostic and therapeutic purposes in patients who had undergone kidney transplant. MATERIALS AND METHODS: We retrospectively evaluated the records of kidney transplant patients for January 1993 to December 2014. Endoscopic retrograde cholangiopancreatography was carried out using an Olympus JF240 duodenoscope (tip outer diameter 12.6 mm, working channel diameter 3.2 mm). The procedures were performed by Department of Anesthesiology staff while the patients were deeply sedated, given a combination of midazolam plus propofol. RESULTS: Data from 21 kidney transplant patients (16 men and 5 women; mean age at endoscopic retrograde cholangiopancreatography 42.6 ± 23.4 y) were evaluated. A total of 23 endoscopic retrograde cholangiopancreatography procedures were performed. The indications were choledocholithiasis in 6 patients (28.6%), common bile duct dilatation plus liver enzyme elevations in 4 patients (19%), liver enzyme elevation alone in 4 (19%), biliary necrotizing pancreatitis in 2 (9.6%), and cholangitis in 5 (23.8%). Hepatobiliary ultrasonography findings showed that 3 patients (14.3%) had absence of gallbladder owing to cholecystectomy, 14 (66.7%) had gallstones, 1 (4.7%) had gallstones with cholecystitis findings, and 3 (14.3%) were normal. Endoscopic retrograde cholangiopancreatography findings were normal in 4 patients (19%), showed cholangitis in 2 (9.6%), choledocholithiasis in 10 (47.6%), bile duct wall irregularities in 2 (9.6%), dilated common bile duct in 2 (9.6%), and cholangiocarcinoma in 1 (4.7%). Sphincterotomy was performed in 16 patients. None of the patients who underwent endoscopic retrograde cholangiopancreatography developed any complications, for example, acute pancreatitis, bleeding, duodenal, or bile duct perforation. CONCLUSIONS: In kidney transplant patients, endoscopic retrograde cholangiopancreatography is safe and able to provide substantial information for managing biliopancreatic diseases.

Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.

Hepatitis B- and hepatitis D-virus-related liver transplant: single-center data.

OBJECTIVES: Hepatitis B and D virus coinfection or superinfection lead to chronic liver disease and have poor treatment results and poor prognosis. After transplant, these patients have difficult problems. We aimed to report long-term data of liver transplant recipients who had hepatitis B and D virus-related chronic liver disease. MATERIALS AND METHODS: This retrospective, longitudinal study included 25 consecutive hepatitis B surface antigen-positive patients with antihepatitis D virus antibodies. Patient data (age, sex, antiviral treatment, posttransplant use of hepatitis B hyperimmunoglobulin and/or nucleoside/nucleotide analogues, the presence of hepatocellular carcinoma, age at transplant, follow-up) were extracted from patient records. RESULTS: Females comprised 32% patients. The median age was 44 years (range, 23-63 y). The serum Hepatitis B envelope antigen level was negative in all patients. At the time of transplant, 4 patients were positive for hepatitis B virus DNA and 11 patients also had hepatocellular carcinoma. Posttransplant follow-up was 59 months (range, 3-120 mo). During follow-up, 4 patients died, 4 patients were lost to follow-up, and 17 patients were alive. Posttransplant survival of patients with hepatocellular carcinoma was 50.45 months (range, 3-84 mo) and without hepatocellular carcinoma was 65.8 months (range, 4-120 mo). There were 3 patients who had acute rejection and were treated successfully with pulse doses of prednisolone. Hyperimmunoglobulin therapy was used in conjunction with oral nucleotide/nucleoside analogues for 12 months (range, 3-24 mo) and then stopped. After transplant, 4 patients had antiviral medicine changed to adefovir or entecavir because of drug resistance, and otherwise all patients remained negative for hepatitis B virus DNA during follow-up. CONCLUSIONS: Patients transplanted for hepatitis B and D virus cirrhosis, even with hepatocellular carcinoma, had favorable prognosis and good longterm results. Close follow-up of patients and effective viral suppression with suitable drugs were key factors for efficient patient care.

Progression of hepatic histopathology in kidney transplant recipients with chronic hepatitis C virus infection and effect of immunosuppression on the course of hepatitis C virus infection.

OBJECTIVES: There is no correlation between alanine aminotransferase levels, viral load, and histologic findings at dialysis in patients with chronic hepatitis C virus infection. Identification of the severity of hepatitis C-related liver disease before transplant could provide valuable data about the risk for liverrelated mortality after transplant. In this study, we aimed to identify the severity of liver disease in endstage renal disease patients with chronic hepatitis C virus infection, the progression of hepatic histopathology after kidney transplant, and whether immunosuppressive therapy affected posttransplant viral replication and hepatic histology. MATERIALS AND METHODS: Antihepatitis C viruspositive kidney transplant recipients (45 patients) enrolled in the study. Liver biopsy was performed in 45 patients before and 16 patients after kidney transplant. Interferon was given to 28 of 45 patients before kidney transplant. Biopsy before and after kidney transplant was performed in 5 of 14 patients. RESULTS: Patients had higher viral load, with genotype 1 predominancy (91%). Sustained viral response was achieved in 14 of 28 patients (50%). The histopathologic features of 45 patients who had pretransplant liver biopsy were as follows: 22 patients had mild hepatocellular injury, 17 patients had mild chronic hepatitis, 5 patients had moderate chronic hepatitis, and 1 patient had serious hepatitis. Follow-up biopsy after kidney transplant (mean, 2 y) in 16 of 45 patients showed that 3 of 16 patients had mild hepatocellular injury, 4 of 16 patients had mild hepatitis, 6 of 16 patients had moderate hepatitis, 2 of 16 patients had serious hepatitis, and 1 patient had cirrhosis. Patients showed neither progression, regression, nor stable liver histology. CONCLUSIONS: Even with worse genotype profiles, chronic hepatitis C virus infection has an indolent progression in patients with end-stage renal disease and kidney transplant. Follow-up biopsies of kidney transplant recipients show reasonable progression during the first 2 years.

The effect of pretransplant chronic hepatitis C virus infection treatment on graft and patient survival in renal transplant recipients.

OBJECTIVES: Studies have demonstrated worse graft and patient survival among hepatitis C virus-positive patients following kidney transplant. Eradication of hepatitis C virus infection before renal transplant with interferon should be considered in hepatitis C virus-infected patients undergoing dialysis who are on the waiting list for transplant. We investigated whether pretransplant hepatitis C virus infection treatment affected graft and patient survival, and we evaluated other contributing factors to these outcomes. MATERIALS AND METHODS: We enrolled 83 antihepatitis C virus-positive patients who were diagnosed with chronic hepatitis C virus infection by serology or histopathology and had renal transplant at Baskent University Ankara Hospital from 1982 to 2013. Data were obtained from patient medical files retrospectively. Patients were divided into 2 groups that had or did not have interferon treatment. RESULTS: In 83 renal transplant patients with chronic hepatitis C virus infection (57 male [69%] and 26 female [31%]), median age was 46 years (range, 26 - 69 y), and most patients were genotype 1-dominant (92%). Interferon monotherapy was received by 30 patients before renal transplant and 28 of 30 patients had long-term follow-up data. There were 14 of 28 patients (50%) who achieved sustained virologic response, and only 1 patient had relapse. Graft survival was significantly lower in patients who had treatment (6 y vs 9 y; P ≤ .003). However, patient survival rates were similar between groups. Patients who had interferon were younger and had longer hemodialysis duration before renal transplant than patients without treatment. Higher viral load was associated with higher mortality which was caused by sepsis. CONCLUSIONS: Patients with posttransplant lymphoproliferative disorder have high incidence of bone marrow involvement and high mortality rates. Therefore, bone marrow examination may be important in the diagnosis and staging evaluation of posttransplant lymphoproliferative disorder.

Panel reactive antibodies in predicting hepatitis C virus treatment outcome in kidney transplant candidates.

OBJECTIVES: Chronic hepatitis C virus infection compromises hemodialysis patients and increases liver-related mortality. Interferon treatment is associated with improved sustained virological response rates and increased risk of graft loss after kidney transplant. This may be related to the development of antihuman leukocyte antigen antibodies, which may be a surrogate marker of potent immune response. We evaluated panel reactive antibody 1 and 2 levels for prediction of sustained viral response in patients with kidney transplant. MATERIALS AND METHODS: In this retrospective cohort study, we reviewed data from hepatitis C virusinfected hemodialysis patients who received interferon treatment before kidney transplant. Panel reactive antibody > 20% was considered positive. Sustained viral response rates for interferon treatment were obtained and compared with panel reactive antibody 1 and 2 values. RESULTS: There were 40 patients (16 female and 24 male patients; mean age, 41.5 y; range, 18-65 y). Sustained viral response rate was 18/40 (45%). Panel reactive antibody 1 was negative in 31 patients and positive in 9 patients. Sustained viral response ratio was not correlated with panel reactive antibody 1 positivity. Panel reactive antibody 2 was negative in 31 patients (sustained viral response: present, 11 patients; absent, 20 patients) and positive in 9 patients (sustained viral response: present, 7 patients; absent, 2 patients). Sustained viral response ratio was significantly correlated with panel reactive antibody 2 positivity. CONCLUSIONS: We showed a correlation between panel reactive antibody 2 positivity and sustained viral response rates that may be a predictive tool for hepatitis C virus treatment response. In patients with other complications that compromise hepatitis C virus treatment, panel reactive antibody 2 may be a surrogate marker for sustained viral response prediction. The induction of cellular immunity may cause clearance of hepatitis C virus infection and formation of high panel reactive antibody 2 levels.

Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New?

Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue.

Successful management of severe acute liver disease related with adult-onset Still's disease in a pregnant patient.

Adult-onset Still's disease is a rare systemic inflammatory disease, which is characterized by varying degrees of liver involvement. Herein we present a rare case of pregnancy onset adult onset Still's disease with severe acute liver disease which worsened after labor. The patient was successfully managed with medical treatment preventing acute liver failure, and is currently in remission from adult onset Still's disease with liver tests that have returned to normal.

Long-term follow-up study in Budd-Chiari syndrome: single-center experience in 22 years.

GOALS: We aimed to present our long-term surveillance experience in patients with Budd-Chiari syndrome (BCS), and we retrospectively evaluated the natural history, results of thrombophilia studies, and the factors related to mortality. BACKGROUND: Primary BCS is a rare form of vascular disease, secondary to underlying thrombophilia. Because of its rarity and heterogeneous nature, there is a scarcity of knowledge about the natural history of the disease. STUDY AND RESULTS: In 22 years, a total of 62 patients with primary BCS were followed in our tertiary hospital. We identified an acquired cause of BCS in 40 out of 62 patients (64.5%), whereas in 6 patients (9.7%), we found no identifiable cause. One or more thrombophilia causes were identified in 56 patients (90.3%). In 19 patients with myeloproliferative disease, 15 had Janus tyrosine kinase 2 mutation analysis and Janus tyrosine kinase 2 positivity was found in 10 patients. In regression analysis, portal vein thrombosis was found to be the only indicator of mortality, with an estimated instantaneous risk of 8.4. CONCLUSIONS: In this study, we present one of the largest series of BCS in the English literature. We have shown that the multifactorial nature of underlying thrombophilia should be thoroughly investigated. In a patient with BCS, a clinician should be alert for the development or coexistence of portal vein thrombosis due to its deleterious effect on mortality.

Red cell distribution width can predict intestinal atrophy in selected patients with celiac disease.

BACKGROUND: Red cell distribution width (RDW) has been shown as a distinctive marker of mortality and morbidity in a wide spectrum of conditions related to systemic inflammation or deficiency of antioxidant nutrients. OBJECTIVE: We aimed to investigate the predictive value of RDW in detection of intestinal atrophy in celiac disease (CD). METHODS: Iron indices and RDW were studied in 49 patients with CD to evaluate the utilization of RDW as a predictive marker for presence of intestinal atrophy. RESULTS: Sixty-nine percent of patients had iron deficiency at initial presentation and 89% had abnormal RDW defined as >14. Receiver operating characteristics curves of RDW has been found to be a predictive of intestinal atrophy at levels higher than 17.25 (68% sensitivity and 85% specificity). In patients with transglutaminase antibody IgA titers >200 U/l, RDW level >17.75 showed 76% sensitivity and 100% specificity for intestinal atrophy. CONCLUSIONS: We suggest that RDW can be used as a surrogate marker of atrophy in patients with iron deficiency and suspected CD. In addition, the sensitivity, specificity, negative and positive predictive values of RDW increases when used in combination with high levels of transglutaminase IgA antibody.

How can portal vein cavernous transformation cause chronic incomplete biliary obstruction?

Biliary disease in the setting of non-cirrhotic portal vein thrombosis (and similarly in portal vein cavernous transformation) can become a serious problem during the evolution of disease. This is mostly due to portal biliary ductopathy. There are several mechanisms that play a role in the development of portal biliary ductopathy, such as induction of fibrosis in the biliary tract (due to direct action of dilated peribiliary collaterals and/or recurrent cholangitis), loss of biliary motility, chronic cholestasis (due to fibrosis or choledocholithiasis) and increased formation of cholelithiasis (due to various factors). The management of cholelithiasis in cases with portal vein cavernous transformation merits special attention. Because of a heterogeneous clinical presentation and concomitant pathophysiological changes that take place in biliary anatomy, diagnosis and therapy can become very complicated. Due to increased incidence and complications of cholelithiasis, standard treatment modalities like sphincterotomy or balloon sweeping of bile ducts can cause serious problems. Cholangitis, biliary strictures and hemobilia are the most common complications that occur during management of these patients. In this review, we specifically discuss important issues about bile stones related to bile duct obstruction in non-cirrhotic portal vein thrombosis and present evidence in the current literature.

Unilobar tapering cirrhosis in a patient with Caroli syndrome associated with an abnormal common bile duct.

Caroli syndrome is a rare condition and is composed of congenital cystic dilatation of the biliary system and congenital hepatic fibrosis. Although many associated conditions are defined and hypothesized to occur concomitantly, due to the rarity of this syndrome, none has proven to be an essential component of this syndrome. In order to investigate a patient presenting with a cholestatic clinical picture, ultrasound, endoscopic retrograde cholangiopancreatography, abdominal computed tomography, liver biopsy, splenoportal venous angiography, and all available liver tests were performed. Upon typical findings, a diagnosis of Caroli syndrome was made and an orthotopic liver transplantation was performed. Investigation of the patient demonstrated multiple intracystic stones mimicking hemangiomatosis in the ultrasound; severe irregularity and narrowing in the main bile duct mimicking sclerosing cholangitis in the endoscopic retrograde cholangiopancreatography; partial portal vein thrombosis with irregularity in the portography; and a unilobar cirrhosis of the left liver lobe while the right lobe demonstrated only congenital hepatic fibrosis in the explanted liver. Caroli syndrome may be associated with main bile duct and portal vein abnormalities. Although the syndrome can be monolobar in nature, a cirrhotic left lobe sparing the right lobe, partially affected by the cirrhotic process, has never been defined. Here, we report a case of Caroli syndrome who had liver transplantation, with very rare and interesting findings of the explanted liver, such as tapering cirrhosis from the left lobe to the right lobe and countless stones in biliary cysts mimicking hemangiomas.

What are the clinical implications of nodular gastritis? Clues from histopathology.

There is no widely accepted histopathological definition for nodular gastritis. In this study we aim to uncover the pathologic entity responsible for the nodular appearance and to find clues about the clinical implications of nodular gastritis. Antral biopsy specimens of 160 patients with nodular gastritis and 133 patients without nodular gastritis were examined by an experienced pathologist for dysplasia, foveolar hyperplasia, inflammatory activity, intraepithelial lymphocytosis, intestinal metaplasia, and lymphoid follicle/aggregate formation, and comparative analysis was performed between the two groups of patients. The presence of intraepithelial lymphocytosis was more frequent in patients with nodular gastritis (P < 0.05). There was no difference between the two groups regarding the other pathological features such as presence of dysplasia, inflammatory activity, intestinal metaplasia, lymphoid hyperplasia, and Helicobacter pylori (H. pylori) infection. Increase of intraepithelial lymphocytes may contribute to formation of macroscopical nodules in this peculiar type of gastritis. Nodular gastritis would not indicate a new therapeutic approach in addition to the current measures for Helicobacter pylori infection.

Capability of capsule endoscopy in detecting small bowel ulcers.

Capsule endoscopy (CE) has proved to be the preferred modality for mucosal pathologies of the small bowel. We evaluated the capability of CE for detecting small bowel ulcers and the contribution of CE in establishing the diagnosis. From a total of 66 patients who had undergone normal upper and lower endoscopy and small bowel follow-through, CE revealed previously undiagnosed ulcer(s) in the small intestines of 22 patients. Final diagnoses of the ulcers of these 22 patients were Crohn's disease (n = 9), Behçet's disease (n = 2), nonspecific jejunoileitis (n = 2), vasculitis (n = 1), gastrointestinal stromal tumor (n = 1), adenocarcinoma (n = 1), lymphoma (n = 1), multiple myeloma (n = 1), Meckel's diverticulum (n = 1) and unknown (n = 3). Capsule endoscopy was extremely useful in establishing the diagnosis. In this study, proximal, distal and diffuse small bowel ulcers were determined at rates of 27.3, 59.0 and 13.7%, respectively. Capsule endoscopy facilitated the detection and assessment of ulcerated mucosal lesions located in the small bowel.

Hepatic granuloma in Turkish adults: a report of 13 cases.

BACKGROUND: Hepatic granuloma (HG) is a well defined histopathological finding with an heterogenous clinical presentation. Diagnosis of a specific clinical entity is not possible every time. Descriptive studies may shed light on the various etiologies also common and distinctive findings among these patients. METHODS: We reviewed the results of the liver biopsies of 592 patients. Characteristics of the patients with HG were extracted from the hospital charts. Laboratory studies included biochemical tests, hepatitis C virus (HCV) antibody, Brucella agglutination tests, tuberculin skin test. According to the diagnostic clues further tests (thoracic computed tomography (CT), ultrasonography, organ biopsy in addition to liver, antimitochondrial antibody, hepatitis B surface (HBs) antigen, venereal disease research laboratory (VDRL)) were performed. RESULTS: HG was found in 13 of the 592 patients (2.2%). Primary biliary cirrhosis (three cases) was the most frequent cause followed by sarcoidosis, miliary tuberculosis and BCGitis (Bacillus Calmette Guerin) (two cases each). Two patients with HG could not be diagnosed. Only three patients had remarkable physical examination findings. Alkaline phosphatase and gamma-glutamyl transpeptidase were the most frequently elevated enzymes. Abdominal ultrasonography provided no specific diagnostic clue in any patient. Localization of the HGs was portal in 6 patients, parenchymal in 5 patients and both portal and parenchymal in 2 patients. Three exitus were due to BCGitis, miliary tuberculosis and fungal infection. CONCLUSIONS: Tuberculosis is still among the most common etiologic factors. BCGitis has a fulminant rather than an indolent course. Abdominal ultrasonography could be used to rule out obstructive jaundice rather than to reach a specific diagnosis. Involvement of portal area by HG in most of the cases might cause obstruction of the biliary canaliculi and elevation of the cholestatic enzymes. Follow up of the difficult cases may be the best approach since the presence of HG was not proved as a bad prognostic factor for any disease.