Digestive System
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Many chronic pancreatitis causing biliary stricture are asymptomatic or associate minimal changes in liver blood tests particularly ALP. In order to call cholestasis we have to see an increase in of usually >3 times ULN of alkaline phosphate (this is about >350-400 U/L)  As long as it does not cause significant cholestasis or cholangitis, there is no indication of biliary draining. IF they associate biliary stones , episodes of repeating infection or biliary pain (his pain seems more due to chronic pancreatitis) then it is justifed to drain the biliary tree.

Despite some increases in ALP, Conservative management with close monitoring is still adequate in this case, as well as recommend complete alcohol abstinence. If his bloods worsen or the bile dilation progresses during the next months, ERCP could be dicussed in a multidisciplinary meeting (risk of stenosis progression and cholestasis vs risk of ERCP adverse events)

-Sporadic Pancreatitis: Episode of acute pancreatitis from any ethiology (Ethanol, Obstructive, drug-related..)  There is no strong identified genetic factors. Incidence is 5-12 per 100000

-Idiopathic Pancreatitis: When Acute recurrent pancreatitis (ARP)  on more than one occasion and no cause identified. SPINK1 and CFTR mutations predispose the pancreas to develop pancreatitis from other genetic or environmental factors. It has been  shown that 16%-23% of patients with apparent idiopathic pancreatitis have SPINK1 mutations, compared with only about 2% of healthy controls. Heterozygotes for CFTR mutations are generally healthy but still have a 3 to 4-fold risk over the general population for pancreatitis.

-Autoimmune pancreatitis: THis is an autoimmune condition with type 1 (lymphoplamocytic infiltrate, IgG 4 associated) and 2 segmental or focal narrowing)  As many autoimune conditions, some multi-gene mutations have been described but no specific strong association genetics proved.

-Hereditary pancreatitis :Rare entity that tends to manifest in early ages. HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. Up to 80% of patients with HP have been found to have a mutation in the PRSS1 gene.  A diagnosis  requires (a) demonstration of a clear pattern of autosomal dominant inheritance in a family and/or (b) finding a known disease-causing variant in the PRSS1 gene. This presentation of disease in a family should be consistent with autosomal dominant inheritance – i.e. two or more individuals with recurrent acute or chronic pancreatitis across two or more generations of a family.   Do not confuse with familial pancreatitis, in which  families with a higher incidence of pancreatitis than expected by chance (2 or more 1st or 2nd degree relative with idiophatic pancreatitis)  but no autosomal dominant pattern or PRSS1 is found

1. True.  Around 80%  of AIH will be either ANA or ASMA+, 8% AMA+, 2% LKM+. 30% SLA+
2.  True. Less than 50% in reduction of transaminases in 4 weeks after treatment is considered Non-response. (Occurs in 17% of treated patients and assoiciates a 7-fold risk of liver related death )
3.  False. Previous guidedlines suggested this parameter, but now we consider response when complete normalisation of transmanisases and IgG.   Liver biopsy is very useful to asses histological response if Modified Ishak hepatitis activity index (mHAI) <4 /18, however histology response lags behind biochemical response by several months: in one  RCT, only 28% and 50% of patients receiving prednisolone±azathioprine achieved histological remission after 6 and 12 months, respectively. Thus, repeat biopsy to confirm remission is not recommended over the first 2 years

4.  True. Since the response criteria are more strict, there will be 20-30% who wont achieve complete biochemical remission.  These scenarios are tricky, we need to compare the overall response, patient adeherence to treatment, considering Azathioprine adeherence and metabolism:  Measuring Thioguanin nucleotides- TGN-  to see that they are in therapeutic range(>220 pmol/8×10) and  Metilmercaptoruine ( MeMP) > 5700 can confirm that the patient is taking the right dose,  Also there are specific situations in which transaminases can remain slightly abnormal due to other causes like MASLD or drug related, and IgG is commonly raised in conditions like cirrhosis.

Check BSG guidelines AIH

According to the  2020 BSG  post-polypectomy surveillance guidelines   we recommend no surveillance if life expectancy is less than 10 y or patient older than 75 yo.  However this can be flexible depending on the patient situation. For example, if histology show incomplete resection margins or colonoscopy was suboptimally prepared then it could be reasonable to repeat the test in 1 year.

If this same case was in a fit and younger patient (e.g  65 yo patient ) then given that we removed 5  adenomas (premalignant) - this would be the cutoff to have another colonoscopy in 3 years

In fact, the majority of the guidelines suggest 3 year follow up if 5 or more small(<10mm)  adenomas are removed.  2020 AGA recommend 3 years followup if 5-10 adenomas, 5 years if 3-4 adenomas and up to 7-10 years if only 1-2 adenomas (or SSL).

For example, if a 65 yo patient had only 4 small adenomas with en bloc resection and good bowel cleaning,  no further surveillance and return to bowel screening according to the British guidelines but would need 5 year colonoscopy according to the AGA guidelines. 

In the guidelines they mention the increasing resistance of  Hpylori strains in the US to Clarithromycin (20-30%)  and Levofloxacin (approaching 40%) , therfore supporting antibiotics with much lower resistance rates (such as amoxicillin, tetracycline, and rifabutin that are all 5%)

That is why this guidelines say Clarithromycin- and levofloxacin-containing treatment regimens should be avoided in the absence of demonstrated macrolide and quinolone susceptibility, respectively.

Clarithromycin- and levofloxacincontaining treatment regimens remain an important option for selected patients, especially treatment-experienced patients with confirmed persistent H. pylori infection with strains that are known to be susceptible to these antibiotics

Vonoprazan is potassium-competitive acid blocker (PCAB) that inhibits the H⁺, K⁺-ATPase enzyme system in a potassium-competitive manner.    This is the same target as PPI but this class  of drugs  are acid-stable and thus do not require enteric coating or optimal dosing administration 30 minutes prior to meals , are more potent acid suppression, rapid onset of action, and long-lasting half-life.   Penicillin dual therapy was superior to lansoprazole-clarithromycin triple therapy among patients with clarithromycin-resistant H. pylori strains (70% vs 32%, P , 0.0001).

When treating with Vonoprazan + Amoxicillin, exceptionally we can add Clarithromycin as first line even in naive patients.

Even though only 10% of hep B infections will become chronic and we have an effective vaccination that can virtually prevent infection, the reality is that hepatitis B incidence and prevalence is very high.  WHO estimates that 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections each year. Maternal-to-newborn perinatal transmission of the virus can be high (70 to 90% in HBeAg-positive-indicating high viral replication-, or 10% to 30% if the mother is HBeAg-negative )

Hepatitis C , despite easy to become chronic (80% of infections) and no effective vaccine, is less common, (Estimated 50 million worldwide) partly because the vertical transmission is low and also because the new  direct-acting antiviral (DAA) tablets are highly effective at clearing the infection in more than 90% , reducing transmission.

See AASLD  and BSG guidelines

Difficult case. In this patient, option A is false- This is a very early stage ≤2cm (BCLC 0)

HCC requieres always an individualised treatment. Knowing that patient is fit and wihtout portal hypertension, he could be amenable for resection. However ablation has been proved to be as effective as surgery with less adverse events, so it would probably be indicated in such as small lesion as first line. The bigger the lesions, the less efficacious ablation is as can leave tumoral tissue untreated. In this case, transplant  certainly could be considered but would not be an ideal first line option as still is <2cm and Child A does not warrant the inclusion in list.

If this HCC was between 2-5cm, treatment could be trasplant (however Child A has per se no indication for transplant, being in the list with modify MELD can be tricky and has risk of tumour progression) surgical resection or ablation, based on radiological features , patient background and preferences

If multifocal HCC,  transplant is ususally the recommended 1st line therapy, whereas TACE/SIRT would be an option in non transplant candidates, unless the lesions are in the same lobe and accesible, in which case occasionally surgical resection can be offered.

If mass>7cm, this surpasses even the Expanded Milan criteria, and we know the risks of HCC invasion, recurrence and mortality after transplant are too high, therefore TACE/ SIRT/ Stereotactic resection or surgical resection are options based on patients features.

It has always been agreed that High grade dysplasia should merit ablation, however clasically LGD would be offered endoscopic surveillance until progressed to HGD. This approach has changed over the last years to the point that Both ESGE and AGA suggest eradication with ablation to prevent progression to HGD/cancer. BSG recommends repeating endoscopy in 6 months and if confirmed again, offering eradication vs 6 -monthly surveillance.  The AGA 2024 guidelines favous ablation over surveillance.

All societies agree that he biopsies should be reviewed by an expert pathologist (ESGE suggest 2 experts) before embarking into eradication.  Remember that the incidence of progression (to HGD or adenoca) is estimated around   9.1%/year  with reported incidence of adenocarcinoma of 0.54% per year. The overall yearly incidence of Eosphageal adenocarcinoma is 0.3% (0.19 in short segment )

Methotrexate, same as Azathioprine or Mercaptopurine, is NOT recommended for inducing remission , but to maintain remission. It can take up to 12 weeks to work However, these immunomodulators should be started earlier when patient is responding to first line treatment, in order to maintain remission and prevent flareups,  especially those with extensive disease or other poor prognostic features (early age at diagnosis, penetrating or stricturing disease, neeed for steroid, high CRP, smoker) should be considered for early introduction of biological therapy (dual biologic plus immunomodulator)

Active Crohn’s first line of treatment is an 8-week course of systemic corticosteroids to induce remission. Budesonide can be used  in mild-moderate case of ileal crohns, but should be escalated to systemic treatment if patient does not response.

Exclusive Enteral Nutrition (EEN) may be used to induce remission in mild to moderate Crohn’s disease patients where avoidance of corticosteroid is desired, and in those who are motivated to adhere strictly to EEN for up to 8 weeks. As this is a young male, this could be a possibility that may be worth exploring with paediatricians , dietitian and surgical team involvement. Howwever the fact that CRP is so high makes this case not  the ideal  candidate as he is already presenting systemic inflammation and there should be a good window of time needed  for this diet to work.

See BSG IBD guidelines 

The proportion of AST to ALT in hepatocytes is about 2.5:1, but because AST is removed from serum by the liver sinusoidal cells twice as quickly (serum half-life t1/2 = 18 hr) compared to ALT (t1/2 = 36 hr), so the resulting serum levels of AST and ALT are about equal in healthy individuals, resulting in a normal AST/ALT ratio around 1. See here.

B6 is more essencial for ALT synthesis than AST, that is why in chronic alcohol (low B6) we will see a reduction of ALT in proportion to AST, increasing the AST/ALT ratio>2